Myocardial deformation in fetuses with coarctation of the aorta: a case-control study.

OBJECTIVE: To study myocardial deformation by speckle tracking echocardiography in fetuses with coarctation of the aorta (CoA) compared with gestational age-matched normal controls. METHODS: This was a retrospective study of 12 fetuses with postnatally confirmed CoA and 12 gestational age-matched controls seen at a tertiary fetal cardiology unit between January 2013 and July 2014. Two-dimensional speckle tracking in standard grayscale four-chamber view of the fetal heart was performed to assess left and right myocardial deformation. Global longitudinal strain, strain rate and velocities, and regional longitudinal strain were analyzed and compared with controls. RESULTS: Median gestational age at echocardiography was 25 + 4 weeks. Fetuses with CoA presented with a narrower, but not shorter, left ventricle when compared with controls (mitral valve diastolic diameter, 5.90 vs 8.50 mm; P = 0.002; left ventricular diastolic length, 16.50 vs 18.50 mm; P = 0.05). Global longitudinal systolic strain (P = 0.004), systolic strain rate (P = 0.01) and diastolic strain rate (P = 0.004) of the left ventricle were significantly lower in fetuses with CoA compared with controls. Similar findings were observed for longitudinal systolic (P = 0.03) and diastolic (P = 0.01) velocities of the left ventricle. Right ventricular parameters were not different between groups. CONCLUSIONS: Fetuses with CoA have lower left ventricular longitudinal systolic strain, systolic strain rate and diastolic strain rate when compared with gestational age-matched control fetuses. These differences in deformation might explain, at least in part, the cardiac asymmetry observed in fetuses with CoA. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Efficient, designable, and broad-bandwidth optical extinction via aspect-ratio-tailored silver nanodisks.

Subwavelength resonators, ranging from single atoms to metallic nanoparticles, typically exhibit a narrow-bandwidth response to optical excitations. We computationally design and experimentally synthesize tailored distributions of silver nanodisks to extinguish light over broad and varied frequency windows. We show that metallic nanodisks are 2-10x more efficient in absorbing and scattering light than common structures, and can approach fundamental limits to broadband scattering for subwavelength particles. We measure broadband extinction per volume that closely approaches theoretical predictions over three representative visible-range wavelength windows, confirming the high efficiency of nanodisks and demonstrating the collective power of computational design and experimental precision for developing new photonics technologies.

What's new: Management of venous leg ulcers: Approach to venous leg ulcers.

Leg ulcerations are a common problem, with an estimated prevalence of 1% to 2% in the adult population. Venous leg ulcers are primarily treated in outpatient settings and often are managed by dermatologists. Recent advances in the diagnosis and treatment of leg ulcers combined with available evidence-based data will provide an update on this topic. A systematized approach and the judicious use of expensive advanced therapeutics are critical. Specialized arterial and venous studies are most commonly noninvasive. The ankle brachial pressure index can be performed with a handheld Doppler unit at the bedside by most clinicians. The vascular laboratory results and duplex Doppler findings are used to identify segmental defects and potential operative candidates. Studies of the venous system can also predict a subset of patients who may benefit from surgery. Successful leg ulcer management requires an interdisciplinary team to make the correct diagnosis, assess the vascular supply, and identify other modifiable factors to optimize healing. The aim of this continuing medical education article is to provide an update on the management of venous leg ulcers. Part I is focused on the approach to venous ulcer diagnostic testing.

What's new: Management of venous leg ulcers: Treating venous leg ulcers.

Venous leg ulcers account for approximately 70% of all leg ulcers and affect 2.2 million Americans annually. After a comprehensive patient and wound assessment, compression therapy remains the cornerstone of standard care. Adjuvant care with topical or systemic agents is used for wounds that do not heal within 4 weeks. Once healed, long-term compression therapy with stockings or surgical intervention will reduce the incidence of recurrence. This continuing medical education article aims to outline optimal management for patients with venous leg ulcers, highlighting the role of a multidisciplinary team in delivering high quality care.

Prenatal diagnosis of left ventricular diverticulum and coarctation of the aorta.

Congenital left ventricular diverticulum (LVD) is a rare abnormality of the myocardium which has been detected previously in the fetus. Lesions have been reported from as early as 12 weeks' gestation but are more commonly detected in the mid-second trimester. Fetal presentation of LVD ranges from an abnormal four-chamber view of the heart, arrhythmia or isolated pericardial effusion to fetal hydrops with associated heart failure. Here, we describe the prenatal diagnosis of an infant with LVD originating from the left ventricular outflow tract associated with coarctation of the aorta. The diagnosis was confirmed postnatally by two-dimensional echocardiography and cardiac magnetic resonance imaging. We hypothesize that the lesion compromised antegrade flow into the transverse aortic arch, which may have contributed to underdevelopment of the aortic arch and subsequently the development of coarctation of the aorta. This is a unique case of LVD and coarctation of the aorta.

Fundamental limits to extinction by metallic nanoparticles.

We show that there are shape-independent upper bounds to the extinction cross section per unit volume of dilute, randomly arranged nanoparticles, given only material permittivity. Underlying the limits are restrictive sum rules that constrain the distribution of quasistatic eigenvalues. Surprisingly, optimally designed spheroids, with only a single quasistatic degree of freedom, reach the upper bounds for four permittivity values. Away from these permittivities, we demonstrate computationally optimized structures that surpass spheroids and approach the fundamental limits.

Near-field electromagnetic theory for thin solar cells.

Current methods for evaluating solar cell efficiencies cannot be applied to low-dimensional structures where phenomena from the realm of near-field optics prevail. We present a theoretical approach to analyze solar cell performance by allowing rigorous electromagnetic calculations of the emission rate using the fluctuation-dissipation theorem. Our approach shows the direct quantification of the voltage, current, and efficiency of low-dimensional solar cells. This approach is demonstrated by calculating the voltage and the efficiency of a GaAs slab solar cell for thicknesses from several microns down to a few nanometers. This example highlights the ability of the proposed approach to capture the role of optical near-field effects in solar cell performance.

Metazoan rDNA enhancer acts by making more genes transcriptionally active.

Enhancers could, in principle, function by increasing the rate of reinitiation on individual adjacent active promoters or by increasing the probability that an adjacent promoter is activated for transcription. We have addressed this issue for the repetitive metazoan rDNA enhancer by microinjecting Xenopus oocytes with enhancer-less and enhancer-bearing genes and determining by EM the frequency that each gene type forms active transcription units and their transcript density. We use conditions where transcription requires the normal rDNA promoter and is stimulated 30-50-fold by the enhancer. (In contrast, at saturating template conditions as used in previous EM studies, an aberrant mode of transcription is activated that is not affected by the rDNA enhancer or by the generally recognized rDNA promoter). The active transcription units on enhancer-less genes are found to be as densely packed with nascent transcripts and polymerases as those on enhancer-bearing genes and on the endogenous rRNA genes. Significantly, the enhancer-bearing genes are approximately 30-50-fold more likely to form such active transcription units than enhancer-less genes, consistent with their amounts of transcript. Complementary studies confirm that the enhancer does not affect elongation rate, the stability of the transcription complex, or transcript half-life. These data demonstrate that the repetitive metazoan rDNA enhancer causes more genes to be actively transcribed and does not alter the reinitiation rate on individual active genes.

Visualization of nucleolar genes.

The presence of extrachromosomal nucleoli in amphibian oocytes has permitted isolation and electron microscopic observation of the genes coding for ribosomal RNA precursor molecules. Visualization of these genes is possible because many precursor molecules are simultaneously synthesized on each gene. Individual genes are separated by stretches of DNA that apparently are not transcribed at the time of synthesis of precursor rRNA in the extrachromosomal nucleoli.

Antibodies to histones and histone-histone complexes: immunochemical evidence for secondary structure in histone 1.

Highly specific antibodies were raised to histone 1 (H 1) and the histone complexes H32-H42 AND H2A-H2B, isolated by salt extraction. Antibody to H1 could detect irreversible conformational changes in acid- or urea-treated H1. The antibodies showed different reactivities with chromosomes as compared to antibodies in acid-extracted histones and should be useful in studies of native chromatin and chromosome structure.

Chromosome mapping in the mouse, fluorescence banding techniques permit assignment of most genetic linkage groups.

Chromosome banding techniques have permitted the identification of every normal chromosome in the mouse, Mus musculus, and the demonstration of strain differences. By identifying the chromosomes involved in a series of translocations, it has been possible to assign 14 of the 19 known linkage groups to 14 different chromosomes. These powerful cytological methods promise to revolutionize cytogenetic studies in higher organisms.

Chromosome localization of highly repetitive human DNA's and amplified ribosomal DNA with restriction enzymes.

Restriction endonucleases cut and partially removed DNA throughout fixed air-dried human metaphase chromosomes. Some enzymes produced a G-banding pattern; some revealed the presence of multiple chromosome-specific classes of highly repetitive DNA in C-band heterochromatin. Enzymes that produced the informative C-band patterns had recognition sequences that were four or five, but not six, base pairs long and did not contain a cytosine-guanine doublet. In both rat and human chromosomes, regions containing amplified ribosomal RNA genes were specifically removed by the restriction endonuclease Msp I.

Visualization of bacterial genes in action.

The morphology of active structural and putative ribosomal RNA genes was observed by electron microscopy after lysis of fragile Escherichia coli cells. Conclusions drawn are: most of the chromosome is not genetically active at any one instant; translation is completely coupled with transcription; the 16S and 23S ribosomal RNA cistrons occur in tandem, in regions which are widely spaced on the chromosome.

Human thymidine kinase gene locus: assignment to chromosome 17 in a hybrid of man and mouse cells.

The human chromosome retained in a hybrid clone derived from human cells and a moluse line deficiemt in thymidine kinase has the quinacrinefluorescence pattern characteristic of chromosome 17.

Mapping the locus of the H-Y gene on the human Y chromosome.

The H-Y locus is on the short arm of the human Y chromosome in most individuals but on the long arm in at least one of 17 individuals with structural abnormalities of the Y.

Impact of provider attire on patient satisfaction in an outpatient dermatology clinic.

Provider attire has been studied as a potential vector for infectious microorganisms in the medical setting as well as a potential factor in patient satisfaction. Our objective was to determine if a change from formal attire to fitted scrubs had a measurable impact on patient satisfaction scores in an outpatient dermatology setting. We designed a 2-year retrospective cohort study of 22 providers in an outpatient dermatology setting who transitioned from formal attire to fitted scrubs and had at least 12 months of patient satisfaction scores (measured by a third-party patient satisfaction survey) before and after the change in attire. The primary outcome was statistically significant change in patient satisfaction scores before and after the institution of fitted scrubs. A total of 3511 completed surveys were evaluated from the 12 months prior to the change in attire (study period 1), and 4191 completed surveys were evaluated in 12 months after the change (study period 2). No significant change was seen in the overall survey responses. A small but statistically significant improvement was noted for several questions in study period 2, which suggested that a change from formal attire to fitted scrubs did not have a strong impact on patient satisfaction scores. Factors beyond provider attire likely have the greatest impact on patient satisfaction.

Electron microscopic study of Saccharomyces cerevisiae rDNA chromatin replication.

An electron microscopic study was made of the replication of rDNA chromatin of Saccharomyces cerevisiae. Two different methods were used to synchronize cells. cdc7-1 cells were raised to a restrictive temperature, whereas A364a cells were blocked with mating factor. Replication bubbles typically opened in the nontranscribed spacers of rDNA repeats in both cell types. The mean position of the center of these bubbles corresponds closely to a position where an autonomously replicating sequence previously has been mapped in an rDNA repeat. Clusters of replication bubbles containing up to four bubbles spaced one to three genes apart were seen opening in early S phase.

Visualization of Drosophila melanogaster chorion genes undergoing amplification.

We visualized by electron microscopy the preferential amplification of Drosophila chorion genes in late-stage follicle cells. Chromatin spreads revealed large clusters of actively transcribed genes of the appropriate size, spacing, and orientation for chorion genes that were expressed with the correct temporal specificity. Occasionally the active genes were observed within or contiguous with intact replicons and replication forks. In every case, our micrographs are consistent with the hypothesis that the central region of each chorion domain contains a replication origin(s) used during the amplification event. In one case, a small replication bubble was observed precisely at the site of the essential region of the X chromosome amplification control element. The micrographs also suggest that forks at either end of a replicon frequently progress very different distances, presumably due to different times in initiation or different rates of movement. It appears that all chorion genes (even those coding for minor proteins) are transcribed in a "fully on" condition, albeit for varied durations, and that if replication fork passage does inactivate a promoter, it does so very transiently. Furthermore, a DNA segment containing one active gene is likely to have an additional active gene(s). Surprisingly, during the time frame of expected maximum activity, approximately half of the chorion sequences appear transcriptionally inactive.

Transcription of mouse rDNA and associated formation of the nucleolus organizer region after gene transfer and amplification in Chinese hamster cells.

Mouse rDNA can initiate transcription by using only Chinese hamster cell components, and this is associated with nucleolus organizer activity. To demonstrate this, we transferred a 3.2-kilobase segment of mouse rDNA containing the promoter, the transcription initiation site, and part of the external transcribed spacer to dihydrofolate reductase-deficient Chinese hamster cells by cotransformation with an abbreviated mouse dhfr gene. Stepwise selection for methotrexate resistance produced sublines in which the mouse rDNA was usually coamplified with the donor dhfr DNA and occupied the same site or sites in the hamster genome, as shown by in situ hybridization. Transcription from mouse rDNA was demonstrated in two such lines, and S1 protection mapping indicated faithful initiation of the transcript. In some cells from both lines, the chromosome segments containing amplified mouse rDNA showed multiple silver-staining regions (i.e., active nucleolus organizers). Although the transferred mouse rDNA was able to use the rDNA transcriptional machinery of the Chinese hamster, the level of transcription was much lower than expected from the rDNA copy number, and a large fraction of each amplified region showed no silver staining. Since the absence of silver staining is generally correlated with the absence of transcription, many copies of the amplified mouse rDNA may have been in a chromatin conformation in which they could not be transcribed. This was not associated with the extensive methylation seen in other amplified, inactive rDNA sequences.

Human ribosomal DNA fragments amplified in hamster cells are transcribed only by RNA polymerase II and are not silver stained.

Cloned human rRNA gene fragments that included the promoter region were introduced into Chinese hamster dihydrofolate reductase-deficient (dhfr-) cells by cotransformation with a dhfr minigene and amplified by selection for methotrexate resistance. The human ribosomal DNA was transcribed by RNA polymerase II, not RNA polymerase I or III. The metaphase chromosome regions containing the transcriptionally active human ribosomal DNA failed to show silver staining.