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Background: Yersinia pestis, a Gram-negative bacterium, is the causative agent of plague. Y. pestis is a zoonotic pathogen that occasionally infects humans and became endemic in the western United States after spreading from California in 1899. Methods: To better understand evolutionary patterns in Y. pestis from the southwestern United States, we sequenced and analyzed 22 novel genomes from New Mexico. Analytical methods included, assembly, multiple sequences alignment, phylogenetic tree reconstruction, genotype-phenotype correlation, and selection pressure. Results: We identified four genes, including Yscp and locus tag YPO3944, which contained codons undergoing negative selection. We also observed 42 nucleotide sites displaying a statistically significant skew in the observed residue distribution based on the year of isolation. Overall, the three genes with the most statistically significant variations that associated with metadata for these isolates were sapA, fliC, and argD. Phylogenetic analyses point to a single introduction of Y. pestis into the United States with two subsequent, independent movements into New Mexico. Taken together, these analyses shed light on the evolutionary history of this pathogen in the southwestern US over a focused time range and confirm a single origin and introduction into North America.

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Chikungunya virus (CHIKV) has been detected sporadically since the 1950s and includes three distinct co-circulating genotypes. In late 2013, the Asian genotype of CHIKV was responsible for the Caribbean outbreak (CO) that rapidly became an epidemic throughout the Americas. There is a limited understanding of the molecular evolution of CHIKV in the Americas during this epidemic. We sequenced 185 complete CHIKV genomes collected mainly from Nicaragua in Central America and Florida in the United States during the 2014-2015 Caribbean/Americas epidemic. Our comprehensive phylogenetic analyses estimated the epidemic history of the Asian genotype and the recent Caribbean outbreak (CO) clade, revealed considerable genetic diversity within the CO clade, and described different epidemiological dynamics of CHIKV in the Americas. Specifically, we identified multiple introductions in both Nicaragua and Florida, with rapid local spread of viruses in Nicaragua but limited autochthonous transmission in Florida in the US. Our phylogenetic analysis also showed phylogeographic clustering of the CO clade. In addition, we identified the significant amino acid substitutions that were observed across the entire Asian genotype during its evolution and examined amino acid changes that were specific to the CO clade. Deep sequencing analysis identified specific minor variants present in clinical specimens below-consensus levels. Finally, we investigated the association between viral phylogeny and geographic/clinical metadata in Nicaragua. To date, this study represents the largest single collection of CHIKV complete genomes during the Caribbean/Americas epidemic and significantly expands our understanding of the emergence and evolution of CHIKV CO clade in the Americas.

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We present a novel tomographic non-local-means based despeckling technique, TNode, for optical coherence tomography. TNode is built upon a weighting similarity criterion derived for speckle in a three-dimensional similarity window. We present an implementation using a two-dimensional search window, enabling the despeckling of volumes in the presence of motion artifacts, and an implementation using a three-dimensional window with improved performance in motion-free volumes. We show that our technique provides effective speckle reduction, comparable with B-scan compounding or out-of-plane averaging, while preserving isotropic resolution, even to the level of speckle-sized structures. We demonstrate its superior despeckling performance in a phantom data set, and in an ophthalmic data set we show that small, speckle-sized retinal vessels are clearly preserved in intensity images en-face and in two orthogonal, cross-sectional views. TNode does not rely on dictionaries or segmentation and therefore can readily be applied to arbitrary optical coherence tomography volumes. We show that despeckled esophageal volumes exhibit improved image quality and detail, even in the presence of significant motion artifacts.

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We report here the whole-genome sequence of 11 Zika virus (ZIKV) samples from six pediatric patients in Nicaragua. Serum samples were collected, and ZIKV was isolated in tissue culture. Both serum and virus isolates were sequenced. The consensus ZIKV genomes are greater than 99% identical to each other.

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BACKGROUND: Qualitative and quantitative flow hemodynamic indexes have been shown to reflect right ventricular (RV) afterload and function in pulmonary hypertension (PH). We aimed to quantify flow hemodynamic formations in pulmonary arteries using 4-dimensional flow cardiac magnetic resonance imaging and the spatial velocity derivatives helicity and vorticity in a heterogeneous PH population. METHODS AND RESULTS: Patients with PH (n=35) and controls (n=10) underwent 4-dimensional flow magnetic resonance imaging study for computation of helicity and vorticity in the main pulmonary artery (MPA), the right pulmonary artery, and the RV outflow tract. Helicity and vorticity were correlated with standard RV volumetric and functional indexes along with MPA stiffness assessed by measuring relative area change. Patients with PH had a significantly decreased helicity in the MPA (8 versus 32 m/s2; P<0.001), the right pulmonary artery (24 versus 50 m/s2; P<0.001), and the RV outflow tract-MPA unit (15 versus 42 m/s2; P<0.001). Vorticity was significantly decreased in patients with PH only in the right pulmonary artery (26 versus 45 1/s; P<0.001). Total helicity computed correlated with the cardiac magnetic resonance imaging-derived ventricular-vascular coupling (-0.927; P<0.000), the RV ejection fraction (0.865; P<0.0001), cardiac output (0.581; P<0.0001), mean pulmonary arterial pressure (-0.581; P=0.0008), and relative area change measured at the MPA (0.789; P<0.0001). CONCLUSIONS: The flow hemodynamic character in patients with PH assessed via quantitative analysis is considerably different when compared with healthy and normotensive controls. A strong association between helicity in pulmonary arteries and ventricular-vascular coupling suggests a relationship between the mechanical and flow hemodynamic domains.

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Clinical advances in the treatment of dentoalveolar defects continue to evolve with the introduction of new innovations in regenerative medicine and tissue bioengineering. Recent developments in tissue engineering are aimed at safely and effectively regenerating a damaged or necrotic area by replenishing its cells and increasing surrounding gene expression. Various techniques have successfully given rise to porous scaffolds being used by clinicians to treat the defect and initiate the repair process. Tissue reconstruction using bioengineered scaffolds is advantageous over traditional autografting, since it prevents the instigation of pain and donor site morbidity while ultimately creating both the environment and machinery needed to induce cell proliferation, migration, and reattachment within the affected area. This review article aims to describe and review the available literature regarding the regenerative capacity of natural polymers used for the treatment of dentoalveolar defects. The repair mechanisms, advantages of protein and polysaccharide derivatives, and the potential of stem cell therapy are discussed.

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Noroviruses are the leading cause of acute gastroenteritis in the United States and are responsible for at least 50 % of acute gastroenteritis outbreaks occurring worldwide each year. In addition, noroviruses have caused outbreaks on cruise ships, in nursing homes and hospitals, and in deployed military personnel, but its role in the etiology of travelers' diarrhea is not well defined. The aim of this review is to describe the role of noroviruses in travelers' diarrhea in terms of epidemiology, current diagnostics, treatment and vaccine development efforts. Studies have shown prevalence rates of noroviruses in travelers' diarrhea cases ranging from 10-65 %. It is likely that norovirus prevalence rates are highly underestimated in travelers' diarrhea due to rapid onset, short duration of the illness, limited availability of laboratory facilities, and the fact that most clinical laboratories lack the diagnostic capability to detect noroviruses in stool. Further, additional studies are needed to accurately determine the true prevalence rates of norovirus as an etiologic agent of diarrhea among travelers to different regions around the world. With the rapid progress in the development of a norovirus vaccine, travelers could serve as an ideal population for future norovirus clinical trials.

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The investigation of deaths of individuals whose bodies are decomposed, mummified, or skeletonized is particularly difficult for medical examiners and medicolegal death investigators. Determination of the cause and manner of death in such cases frequently requires consultation with experts in a variety of disciplines in the forensic sciences and necessitates correlation of the autopsy results, scene investigation, medical and social history of the deceased, and laboratory studies. The authors report an unusual case of an apparent homicide/suicide involving 2 individuals and a canine that went undetected for almost 4 years. Determination of the cause and manner of death in these cases involved a multidisciplinary, intercontinental investigation and necessitated the performance of toxicologic studies on specimens not commonly analyzed. These cases illustrate the importance of the multidisciplinary approach to medicolegal death investigations and the necessity of considering nontraditional sources of potential information and specimens for laboratory analysis in selected cases.

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Nineteen children with hypomelanosis of Ito are described. Fourteen were developmentally delayed and nine had a history of seizures. Hemihypertrophy was present in four patients, syndactyly in three, and scoliosis in one. Twelve of the children had abnormal electroencephalograms and nine had abnormal brain scans, four with appearances suggestive of abnormal neuronal migration. There is very little evidence, either from the literature or from our patients, that the disease is inherited. The pattern of the cutaneous lesions suggests that the condition may result from the presence of two different cell populations as a result of mosaicism.

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