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Genetic Consequences of Pleistocene Sea-Level Change on Hawaiian Megalagrion Damselflies. - The Journal of heredity
The Hawaiian Islands have long been an important laboratory for evolutionary research because their geological histories offer many natural experiments. For example, the Maui Nui complex, 4 islands that have been repeatedly connected and separated by fluctuating sea levels, lie near Hawaii Island, which has never been connected to another island. Here, we examine the genetic consequences of fluctuating island areas and connectivity using microsatellite analysis of 2 widespread, endemic Hawaiian damselflies. We screened 152 Megalagrion xanthomelas individuals from 5 islands at 14 loci and 34 Megalagrion pacificum from 3 islands at 11 loci to explore dispersal patterns and genetic diversity. Our data suggest that Pleistocene fluctuations in sea level alternated between creating land bridges that facilitated gene flow between once and future islands, and ocean channels that inhibited dispersal. Furthermore, interglacial periods of high sea stands likely reduced suitable habitat availability, causing the loss of genetic diversity on Maui Nui due to bottlenecks and founder events. Finally, we propose that gene flow from Molokai to Lanai may be enhanced by assisted dispersal from the trade winds that are channeled between volcanoes on western Maui and eastern Molokai. Our results emphasize the importance of variable microevolutionary processes in Hawaiian biogeography.Â© The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. - PLoS medicine
Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes.We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naÃ¯ve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05-1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06-1.25), North America (OR = 1.19; 95% CI: 1.12-1.26), Europe (OR = 1.07; 95% CI: 1.01-1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12-1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92-1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positionsâ€”a proxy for recent infectionâ€”yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMsâ€”K101E, K103N, Y181C, and G190Aâ€”accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling.Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.
Transcriptional activity, chromosomal distribution and expression effects of transposable elements in Coffea genomes. - PloS one
Plant genomes are massively invaded by transposable elements (TEs), many of which are located near host genes and can thus impact gene expression. In flowering plants, TE expression can be activated (de-repressed) under certain stressful conditions, both biotic and abiotic, as well as by genome stress caused by hybridization. In this study, we examined the effects of these stress agents on TE expression in two diploid species of coffee, Coffea canephora and C. eugenioides, and their allotetraploid hybrid C. arabica. We also explored the relationship of TE repression mechanisms to host gene regulation via the effects of exonized TE sequences. Similar to what has been seen for other plants, overall TE expression levels are low in Coffea plant cultivars, consistent with the existence of effective TE repression mechanisms. TE expression patterns are highly dynamic across the species and conditions assayed here are unrelated to their classification at the level of TE class or family. In contrast to previous results, cell culture conditions per se do not lead to the de-repression of TE expression in C. arabica. Results obtained here indicate that differing plant drought stress levels relate strongly to TE repression mechanisms. TEs tend to be expressed at significantly higher levels in non-irrigated samples for the drought tolerant cultivars but in drought sensitive cultivars the opposite pattern was shown with irrigated samples showing significantly higher TE expression. Thus, TE genome repression mechanisms may be finely tuned to the ideal growth and/or regulatory conditions of the specific plant cultivars in which they are active. Analysis of TE expression levels in cell culture conditions underscored the importance of nonsense-mediated mRNA decay (NMD) pathways in the repression of Coffea TEs. These same NMD mechanisms can also regulate plant host gene expression via the repression of genes that bear exonized TE sequences.
Increased susceptibility of Cantagalo virus to the antiviral effect of ST-246Â®. - Antiviral research
Cantagalo virus (CTGV) is the etiologic agent of a pustular disease in dairy cows and dairy workers in Brazil with important economical and occupational impacts. Nevertheless, no antiviral therapy is currently available. ST-246 is a potent inhibitor of orthopoxvirus egress from cells and has proved its efficacy in cell culture and in animal models. In this work, we evaluated the effect of ST-246 on CTGV replication. Plaque reduction assays indicated that CTGV is 6-38 times more susceptible to the drug than VACV-WR and cowpox virus, respectively, with an EC50 of 0.0086Î¼M and a selective index of >11,600. The analysis of Î²-gal activity expressed by recombinant viruses in the presence of ST-246 confirmed these results. In addition, ST-246 had a greater effect on the reduction of CTGV spread in comet tail assays and on the production of extracellular virus relative to VACV-WR. Infection of mice with CTGV by tail scarification generated primary lesions at the site of scarification that appeared less severe than those induced by VACV-WR. Animals infected with CTGV and treated with ST-246 at 100mg/kg for 5days did not develop primary lesions and virus yields were inhibited by nearly 98%. In contrast, primary lesions induced by VACV-WR were not affected by ST-246. The analysis of F13 (p37) protein from CTGV revealed a unique substitution in residue 217 (D217N) not found in other orthopoxviruses. Construction of recombinant VACV-WR containing the D217N polymorphism did not lead to an increase in the susceptibility to ST-246. Therefore, it is still unknown why CTGV is more susceptible to the antiviral effects of ST-246 compared to VACV-WR. Nonetheless, our data demonstrates that ST-246 is a potent inhibitor of CTGV replication that should be further evaluated as a promising anti-CTGV therapy.Copyright Â© 2012 Elsevier B.V. All rights reserved.
International Values of Central Pachymetry in Normal Subjects by Rotating Scheimpflug Camera. - Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)
In corneal refractive surgery, postoperative ectasia risk assessment routinely includes pachymetric analysis at the apex and thinnest point. We examined whether these data differ worldwide and constructed preliminary country-specific normative thresholds.This was a multicenter, cross-sectional study.Using the Pentacam Eye Scanner (OCULUS GmbH, Wetzlar, Germany), we examined 1 randomly selected eye from each of 555 normal adults (8 countries, 6 continents), measuring the thinnest point location, central pachymetry (thinnest point, pupillary center, and apex), and the apex-thinnest point difference. International differences were assessed by 1-way analysis of variance. Normative thresholds were defined by 2- and 3-SD gates or Tukey method.The thinnest point averaged 0.44 mm temporal and 0.29 mm inferior to the apex. Individual thinnest points located more than 1.0 mm inferior represented fewer than 0.5% of normal corneas (>0.76 mm in the US subgroup). The mean thinnest-point pachymetry was 536 Î¼m overall, and values less than 469 or 435 Î¼m (-2 or -3 SD, respectively) would be expected in less than 2.5% or 0.15% of normal corneas, respectively. The thinnest-point pachymetry averaged 2 to 3 Î¼m thinner than apical (range, 0-32 Î¼m). Differences of greater than 8.5 Î¼m would be expected in less than 0.5% of normal corneas overall.International differences were largely clinically insignificant. Nevertheless, it remains preferable to establish racial/geographic-specific normative values. We defined preliminary generalized and country-specific thresholds useful to the corneal refractive surgeon for identifying potentially abnormal corneas based on common pachymetric parameters, particularly the thinnest point by tomography.
Colorado Plateau magmatism and uplift by warming of heterogeneous lithosphere. - Nature
The forces that drove rock uplift of the low-relief, high-elevation, tectonically stable Colorado Plateau are the subject of long-standing debate. While the adjacent Basin and Range province and Rio Grande rift province underwent Cenozoic shortening followed by extension, the plateau experienced approximately 2 km of rock uplift without significant internal deformation. Here we propose that warming of the thicker, more iron-depleted Colorado Plateau lithosphere over 35-40 Myr following mid-Cenozoic removal of the Farallon plate from beneath North America is the primary mechanism driving rock uplift. In our model, conductive re-equilibration not only explains the rock uplift of the plateau, but also provides a robust geodynamic interpretation of observed contrasts between the Colorado Plateau margins and the plateau interior. In particular, the model matches the encroachment of Cenozoic magmatism from the margins towards the plateau interior at rates of 3-6 km Myr(-1) and is consistent with lower seismic velocities and more negative Bouguer gravity at the margins than in the plateau interior. We suggest that warming of heterogeneous lithosphere is a powerful mechanism for driving epeirogenic rock uplift of the Colorado Plateau and may be of general importance in plate-interior settings.
Vancomycin administration: mistakes made by nursing staff. - Nursing standard (Royal College of Nursing (Great Britain) : 1987)
To identify the number and types of errors made by assistant and technical nurses when administering intravenous (IV) vancomycin.Preparation and IV administration of 143 doses of vancomycin by 55 assistant and technical nurses were observed in four acute wards (three adult and one paediatric) in a public university hospital in Brazil. Non-participant observers completed a structured checklist for each dose.A total of 27 (19%) doses were administered correctly and 116 (81%) incorrectly. There were 268 errors of four types: (i) incorrect dose; (ii) improper preparation of a dose; (iii) inadequate administration technique; and (iv) infusion at an incorrect rate. For 13 of 143 (9%) doses, errors occurred in all four aspects of administration. Errors were observed on all four wards.The high incidence of suboptimal administration of vancomycin observed is a cause for concern. Focused education and safety measures have been introduced and their impact is being evaluated.
The Cenozoic palaeoenvironment of the Arctic Ocean. - Nature
The history of the Arctic Ocean during the Cenozoic era (0-65 million years ago) is largely unknown from direct evidence. Here we present a Cenozoic palaeoceanographic record constructed from >400 m of sediment core from a recent drilling expedition to the Lomonosov ridge in the Arctic Ocean. Our record shows a palaeoenvironmental transition from a warm 'greenhouse' world, during the late Palaeocene and early Eocene epochs, to a colder 'icehouse' world influenced by sea ice and icebergs from the middle Eocene epoch to the present. For the most recent approximately 14 Myr, we find sedimentation rates of 1-2 cm per thousand years, in stark contrast to the substantially lower rates proposed in earlier studies; this record of the Neogene reveals cooling of the Arctic that was synchronous with the expansion of Greenland ice (approximately 3.2 Myr ago) and East Antarctic ice (approximately 14 Myr ago). We find evidence for the first occurrence of ice-rafted debris in the middle Eocene epoch (approximately 45 Myr ago), some 35 Myr earlier than previously thought; fresh surface waters were present at approximately 49 Myr ago, before the onset of ice-rafted debris. Also, the temperatures of surface waters during the Palaeocene/Eocene thermal maximum (approximately 55 Myr ago) appear to have been substantially warmer than previously estimated. The revised timing of the earliest Arctic cooling events coincides with those from Antarctica, supporting arguments for bipolar symmetry in climate change.
Autosomal dominant retinitis pigmentosa (adRP): exclusion of a gene from three mapped loci provides evidence for the existence of a fourth locus. - Human molecular genetics
Retinitis Pigmentosa (RP) is a group of inherited retinopathies which affect approximately 1 in 4,000 individuals. The disorder can be classified on the basis of inheritance; dominant, recessive and X-linked forms have been well documented. The existence of genetic heterogeneity within autosomal dominant RP (adRP) had been previously demonstrated. As a result of extensive linkage studies in 2 large Irish families and 1 American pedigree three adRP genes have been mapped. adRP genes have been localised to chromosome 3q close to the rod photoreceptor gene, rhodopsin; to chromosome 6p close to another transmembrane photoreceptor gene, peripherin/RDS and to the pericentric region of chromosome 8, although the causative gene in this region has not yet been identified. Here we report the results of a linkage study in a Spanish family, who exhibit an early-onset form of adRP. The adRP gene segregating in this family has been excluded from the three known adRP loci on chromosomes 3q, 6p and 8 using a series of both intragenic microsatellite markers from the rhodopsin and peripherin/RDS genes and markers flanking the three known loci. These results provide definitive evidence for the existence of a fourth adRP locus, further emphasising the genetic heterogeneity that exists within adRP.
New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk. - Nature communications
To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 Ã— 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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