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Find video protocols related to scientific articles indexed in Pubmed.
Structural effect of the Asp345a insertion in penicillin-binding protein 2 from penicillin-resistant strains of N. gonorrhoeae.
Biochemistry
PUBLISHED: 11-19-2014
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A hallmark of penicillin-binding protein 2 (PBP2) from penicillin-resistant strains of N. gonorrhoeae is insertion of an aspartate after position 345. The insertion resides on a loop near the active site and is immediately adjacent to an existing aspartate (Asp346) that forms a functionally important hydrogen bond with Ser363 of the SxN conserved motif. Insertion of other amino acids, including Glu and Asn, can also lower the rate of acylation by penicillin, but these insertions abolish transpeptidase function. Although the kinetic consequences of the Asp insertion are well established, how it impacts the structure of PBP2 is unknown. Here, we report the 2.2 Å resolution crystal structure of a truncated construct of PBP2 containing all five mutations present in PBP2 from the penicillin-resistant strain 6140, including the Asp insertion. Commensurate with the strict specificity for the Asp insertion over similar amino acids, the insertion does not cause disordering of the structure, but rather induces localized flexibility in the ?2c-?2d loop. The crystal structure resolves the ambiguity as to whether the insertion is Asp345a or Asp346a (due to the adjacent Asp) because the hydrogen bond between Asp346 and Ser362 is preserved and the insertion is therefore Asp346a. The side chain of Asp346a projects directly toward the ?-lactam-binding site near Asn364 of the SxN motif. The Asp insertion may lower acylation by sterically impeding binding of antibiotic or by hindering breakage of the ?-lactam ring during acylation due to the negative charge of its side chain.
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Impact of reversed phase column pairs in comprehensive two-dimensional liquid chromatography.
J Chromatogr A
PUBLISHED: 08-13-2014
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A major issue in optimizing the resolving power of two-dimensional chromatographic separations is the choice of the two phases so as to maximize the distribution of the analytes over the separation space. In this work, we studied the choice of appropriate reversed phases to use in on-line comprehensive two-dimensional liquid chromatography (LC×LC). A set of four chemically different conventional bonded reversed phases was used in the first dimension. The second dimension column was either a conventional bonded C18 phase or a carbon-clad phase (CCP). The LC×LC chromatograms and contour plots were all rather similar indicating that the selectivities of the two phases were also similar regardless of the reverse phase column used in the first dimension. Further, the spatial coverage seen with all four first dimension stationary phases when paired with a second dimension C18 phase were low and the retention times were strongly correlated. However, when the C18 column was replaced with the CCP column much improved separations were observed with higher spatial coverages, greater orthogonalities and significant increases in the number of observed peaks.
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Microsurgical Breast Reconstruction in Thin Patients: The Impact of Low Body Mass Indices.
J Reconstr Microsurg
PUBLISHED: 06-09-2014
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Background?The purpose of this investigation was to examine patients with low body mass index (BMI) regarding the feasibility to perform autologous breast reconstruction in such patients, as well as to determine optimal donor sites and evaluate outcomes accordingly. Patients and Methods?All patients undergoing microsurgical breast reconstruction were divided into three cohorts based on BMI. Group 1 included patients with BMI greater than or equal to 22 kg/m(2) and was defined "low-normal BMI." Patients with BMI 22 to 25 kg/m(2) were placed in Group 2, labeled as "high-normal BMI." Group 3, defined as "overweight," included patients with BMI greater than 25 kg/m(2), but less than 30 kg/m(2). Patients were then analyzed based on demographics, breast cancer history, intraoperative details, complications, and revisionary surgeries. F-tests, chi-square goodness-of-fit tests, and Freeman-Halton extension of the Fisher exact tests were used for statistical analysis. Results?During the study period, a total of 259 reconstructions were performed. Group 1 included 30 patients (n?=?49 flaps), Group 2 included 58 patients (n?=?98 flaps), and Group 3 included 69 patients (n?=?112 flaps). Patients undergoing nipple-areolar sparing mastectomy were more likely to be in Groups 1 (39% [n?=?19]) and 2 (37% [n?=?37]) as compared with Group 3 (14.2% [n?=?16]) (p?
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Altered hepatic sulfur metabolism in cystathionine ?-synthase-deficient homocystinuria: regulatory role of taurine on competing cysteine oxidation pathways.
FASEB J.
PUBLISHED: 06-04-2014
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Cystathionine ?-synthase-deficient homocystinuria (HCU) is a serious life-threatening inborn error of sulfur metabolism with poorly understood pathogenic mechanisms. We investigated the effect of HCU on hepatic cysteine oxidation in a transgenic mouse model of the disease. Cysteine dioxygenase (CDO) protein levels were 90% repressed without any change in mRNA levels. Cysteinesulfinic acid decarboxylase (CSAD) was induced at both the mRNA (8-fold) and protein (15-fold) levels. Cysteine supplementation normalized CDO protein levels without reversing the induction of CSAD. Regulatory changes in CDO and CSAD expression were proportional to homocysteine elevation, indicating a possible threshold effect. Hepatic and blood taurine levels in HCU animals were decreased by 21 and 35%, respectively, and normalized by cysteine supplementation. Expression of the cytoplasmic (GOT1) and mitochondrial (GOT2) isoforms of glutamic-oxaloacetic transaminase were repressed in HCU animals by 86 and 30%, respectively. HCU induced regulatory changes in CSAD, CDO, and GOT1 expression were normalized by taurine supplementation, indicating that cysteine is not the only sulfur compound that regulates hepatic cysteine oxidation. Collectively, our results indicate that HCU induces significant alterations of sulfur metabolism with the potential to contribute to pathogenesis and that cysteine and taurine have the potential to serve as adjunctive treatments in this disease.-Jiang, H., Stabler, S. P., Allen, R. H., Abman, S. H., Maclean, K. N. Altered hepatic sulfur metabolism in cystathionine ?-synthase-deficient homocystinuria: regulatory role of taurine on competing cysteine oxidation pathways.
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Autologous Breast Reconstruction: Preoperative Magnetic Resonance Angiography for Perforator Flap Vessel Mapping.
J Reconstr Microsurg
PUBLISHED: 05-29-2014
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Background?Selection of a vascular pedicle for autologous breast reconstruction is time consuming and depends on visual evaluation during the surgery. Preoperative imaging of donor site for mapping the perforator artery anatomy greatly improves the efficiency of perforator selection and significantly reduces the operative time. In this article, we present our experience with magnetic resonance angiography (MRA) for perforator vessel mapping including MRA technique and interpretation. Methods?We have performed over 400 MRA examinations from August 2008 to August 2013 at our institution for preoperative imaging of donor site for mapping the perforator vessel anatomy. Using our optimized imaging protocol with blood pool magnetic resonance imaging contrast agents, multiple donor sites can be imaged in a single MRA examination. Following imaging using the postprocessing and reporting tool, we estimated incidence of commonly used perforators for autologous breast reconstruction. Results?In our practice, anterior abdominal wall tissue is the most commonly used donor site for perforator flap breast reconstruction and deep inferior epigastric artery perforators are the most commonly used vascular pedicle. A thigh flap, based on the profunda femoral artery perforator has become the second most used flap at our institution. In addition, MRA imaging also showed evidence of metastatic disease in 4% of our patient subset. Conclusion?Our MRA technique allows the surgeons to confidently assess multiple donor sites for the best perforator and flap design. In conclusion, a well-performed MRA with specific postprocessing provides an accurate method for mapping perforator vessel, at the same time avoiding ionizing radiation.
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Cervical radiofrequency neurotomy reduces psychological features in individuals with chronic whiplash symptoms.
Pain Physician
PUBLISHED: 05-23-2014
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Individuals with chronic whiplash associated disorder (WAD) demonstrate various psychological features. It has previously been demonstrated that cervical radiofrequency neurotomy (cRFN) resolves psychological distress and anxiety. It is unknown if cRFN also improves or reduces a broader spectrum of psychological substrates now commonly identified in chronic whiplash, such as post-traumatic stress disorder (PTSD) and pain catastrophizing.
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Serious hepatic complications of selective internal radiation therapy with yttrium-90 microsphere radioembolization for unresectable liver tumors.
Asia Pac J Clin Oncol
PUBLISHED: 05-11-2014
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Selective internal radiation therapy with yttrium-90 microsphere radioembolization has been used to treat unresectable liver tumors and its acute toxicity has been well described. Subacute and long-term hepatic complications related to radioembolization however may be underreported in the literature. This retrospective study describes the incidence and sequelae of serious hepatic complications in patients who underwent radioembolization for unresectable liver tumors.
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The broad-spectrum antiviral compound ST-669 restricts chlamydial inclusion development and bacterial growth and localizes to host cell lipid droplets within treated cells.
Antimicrob. Agents Chemother.
PUBLISHED: 04-28-2014
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Novel broad-spectrum antimicrobials are a critical component of a strategy for combating antibiotic-resistant pathogens. In this study, we explored the activity of the broad-spectrum antiviral compound ST-669 for activity against different intracellular bacteria and began a characterization of its mechanism of antimicrobial action. ST-669 inhibits the growth of three different species of chlamydia and the intracellular bacterium Coxiella burnetii in Vero and HeLa cells but not in McCoy (murine) cells. The antichlamydial and anti-C. burnetii activity spectrum was consistent with those observed for tested viruses, suggesting a common mechanism of action. Cycloheximide treatment in the presence of ST-669 abrogated the inhibitory effect, demonstrating that eukaryotic protein synthesis is required for tested activity. Immunofluorescence microscopy demonstrated that different chlamydiae grow atypically in the presence of ST-669, in a manner that suggests the compound affects inclusion formation and organization. Microscopic analysis of cells treated with a fluorescent derivative of ST-669 demonstrated that the compound localized to host cell lipid droplets but not to other organelles or the host cytosol. These results demonstrate that ST-669 affects intracellular growth in a host-cell-dependent manner and interrupts proper development of chlamydial inclusions, possibly through a lipid droplet-dependent process.
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Identification of specific corrinoids reveals corrinoid modification in dechlorinating microbial communities.
Environ. Microbiol.
PUBLISHED: 04-16-2014
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Cobalamin and other corrinoids are essential cofactors for many organisms. The majority of microbes with corrinoid-dependent enzymes do not produce corrinoids de novo, and instead must acquire corrinoids produced by other organisms in their environment. However, the profile of corrinoids produced in corrinoid-dependent microbial communities, as well as the exchange and modification of corrinoids among community members have not been well studied. In this study, we applied a newly developed liquid chromatography tandem mass spectrometry-based corrinoid detection method to examine relationships among corrinoids, their lower ligand bases and specific microbial groups in microbial communities containing Dehalococcoides mccartyi that has an obligate requirement for benzimidazole-containing corrinoids for trichloroethene respiration. We found that p-cresolylcobamide ([p-Cre]Cba) and cobalamin were the most abundant corrinoids in the communities. It suggests that members of the family Veillonellaceae are associated with the production of [p-Cre]Cba. The decrease of supernatant-associated [p-Cre]Cba and the increase of biomass-associated cobalamin were correlated with the growth of D. mccartyi by dechlorination. This supports the hypothesis that D. mccartyi is capable of fulfilling its corrinoid requirements in a community through corrinoid remodelling, in this case, by importing extracellular [p-Cre]Cba and 5,6-dimethylbenzimidazole (DMB) (the lower ligand of cobalamin), to produce cobalamin as a cofactor for dechlorination. This study also highlights the role of DMB, the lower ligand produced in all of the studied communities, in corrinoid remodelling. These findings provide novel insights on roles played by different phylogenetic groups in corrinoid production and corrinoid exchange within microbial communities. This study may also have implications for optimizing chlorinated solvent bioremediation.
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The effects of indexical and phonetic variation on vowel perception in typically developing 9- to 12-year-old children.
J. Speech Lang. Hear. Res.
PUBLISHED: 04-02-2014
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PURPOSE The purpose of this study was to investigate how linguistic knowledge interacts with indexical knowledge in older children's perception under demanding listening conditions created by extensive talker variability. METHOD Twenty-five 9- to 12-year-old children, 12 from North Carolina (NC) and 13 from Wisconsin (WI), identified 12 vowels in isolated /hVd/ words produced by 120 talkers representing the 2 dialects (NC and WI), both genders, and 3 age groups (generations) of residents from the same geographic locations as the listeners. RESULTS Identification rates were higher for responses to talkers from the same dialect as the listeners and for female speech. Listeners were sensitive to systematic positional variations in vowels and their dynamic structure (formant movement) associated with generational differences in vowel pronunciation resulting from sound change in a speech community. Overall identification rate was 71.7%, which is 8.5% lower than for the adults responding to the same stimuli in Jacewicz and Fox (2012). CONCLUSION Typically developing older children were successful in dealing with both phonetic and indexical variation related to talker dialect, gender, and generation. They were less consistent than the adults, most likely because of less efficient encoding of acoustic-phonetic information in the speech of multiple talkers and relative inexperience with indexical variation.
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Sustainable growth of Dehalococcoides mccartyi 195 by corrinoid salvaging and remodeling in defined lactate-fermenting consortia.
Appl. Environ. Microbiol.
PUBLISHED: 01-24-2014
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Corrinoids are essential cofactors of reductive dehalogenases in Dehalococcoides mccartyi, an important bacterium in bioremediation, yet sequenced D. mccartyi strains do not possess the complete pathway for de novo corrinoid biosynthesis. Pelosinus sp. and Desulfovibrio sp. have been detected in dechlorinating communities enriched from contaminated groundwater without exogenous cobalamin corrinoid. To investigate the corrinoid-related interactions among key members of these communities, we constructed consortia by growing D. mccartyi strain 195 (Dhc195) in cobalamin-free, trichloroethene (TCE)- and lactate-amended medium in cocultures with Desulfovibrio vulgaris Hildenborough (DvH) or Pelosinus fermentans R7 (PfR7) and with both in tricultures. Only the triculture exhibited sustainable dechlorination and cell growth when a physiological level of 5,6-dimethylbenzimidazole (DMB), the lower ligand of cobalamin, was provided. In the triculture, DvH provided hydrogen while PfR7 provided corrinoids to Dhc195, and the initiation of dechlorination and Dhc195 cell growth was highly dependent on the growth of PfR7. Corrinoid analysis indicated that Dhc195 imported and remodeled the phenolic corrinoids produced by PfR7 into cobalamin in the presence of DMB. Transcriptomic analyses of Dhc195 showed the induction of the CbiZ-dependent corrinoid-remodeling pathway and BtuFCD corrinoid ABC transporter genes during corrinoid salvaging and remodeling. In contrast, another operon annotated to encode a putative iron/cobalamin ABC transporter (DET1174-DET1176) was induced when cobalamin was exogenously provided. Interestingly, a global upregulation of phage-related genes was observed when PfR7 was present. These findings provide insights into both the gene regulation of corrinoid salvaging and remodeling in Dhc195 when it is grown without exogenous cobalamin and microbe-to-microbe interactions in dechlorinating microbial communities.
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Combination therapy accelerates diabetic wound closure.
PLoS ONE
PUBLISHED: 01-01-2014
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Non-healing foot ulcers are the most common cause of non-traumatic amputation and hospitalization amongst diabetics in the developed world. Impaired wound neovascularization perpetuates a cycle of dysfunctional tissue repair and regeneration. Evidence implicates defective mobilization of marrow-derived progenitor cells (PCs) as a fundamental cause of impaired diabetic neovascularization. Currently, there are no FDA-approved therapies to address this defect. Here we report an endogenous PC strategy to improve diabetic wound neovascularization and closure through a combination therapy of AMD3100, which mobilizes marrow-derived PCs by competitively binding to the cell surface CXCR4 receptor, and PDGF-BB, which is a protein known to enhance cell growth, progenitor cell migration and angiogenesis.
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The Evolution of Perforator Flap Breast Reconstruction: Twenty Years after the First DIEP Flap.
J Reconstr Microsurg
PUBLISHED: 10-25-2013
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It is over 20 years since the inaugural deep inferior epigastric perforator (DIEP) flap breast reconstruction. We review the type of flap utilized and indications in 2,850 microvascular breast reconstruction over the subsequent 20 years in the senior authors practice (Robert J. Allen). Data were extracted from a personal logbook of all microsurgical free flap breast reconstructions performed between August 1992 and August 2012. Indication for surgery; mastectomy pattern in primary reconstruction; flap type, whether unilateral or bilateral; recipient vessels; and adjunctive procedures were recorded. The DIEP was the most commonly performed flap (66%), followed by the superior gluteal artery perforator flap (12%), superficial inferior epigastric artery perforator flap (9%), inferior gluteal artery perforator flap (6%), profunda artery perforator flap (3%), and transverse upper gracilis flap (3%). Primary reconstruction accounted for 1,430 flaps (50%), secondary 992 (35%), and tertiary 425 (15%). As simultaneous bilateral reconstructions, 59% flaps were performed. With each flap, there typically ensues a period of enthusiasm which translated into surge in flap numbers. However, each flap has its own nuances and characteristics that influence patient and physician choice. Of note, each newly introduced flap, either buttock or thigh, results in a sharp decline in its predecessor. In this practice, the DIEP flap has remained the first choice in autologous breast reconstruction.
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Cervical Radiofrequency Neurotomy Reduces Central Hyperexcitability and Improves Neck Movement in Individuals with Chronic Whiplash.
Pain Med
PUBLISHED: 10-18-2013
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This study aims to determine if cervical medial branch radiofrequency neurotomy reduces psychophysical indicators of augmented central pain processing and improves motor function in individuals with chronic whiplash symptoms.
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Pregnancy alters choline dynamics: results of a randomized trial using stable isotope methodology in pregnant and nonpregnant women.
Am. J. Clin. Nutr.
PUBLISHED: 10-16-2013
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Although biomarkers of choline metabolism are altered by pregnancy, little is known about the influence of human pregnancy on the dynamics of choline-related metabolic processes.
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Buried flap reconstruction after nipple-sparing mastectomy: advancing toward single-stage breast reconstruction.
Plast. Reconstr. Surg.
PUBLISHED: 10-01-2013
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Recent evolutions of oncologic breast surgery and reconstruction now allow surgeons to offer the appropriate patients a single-stage, autologous tissue reconstruction with the least donor-site morbidity. The authors present their series of buried free flaps in nipple-sparing mastectomies as proof of concept, and to explore indications, techniques, and early outcomes from their series.
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Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis.
Ann Fam Med
PUBLISHED: 09-11-2013
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Cinnamon has been studied in randomized controlled trials (RCTs) for its glycemic-lowering effects, but studies have been small and show conflicting results. A prior meta-analysis did not show significant results, but several RCTs have been published since then. We conducted an updated systematic review and meta-analysis of RCTs evaluating cinnamons effect on glycemia and lipid levels.
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Nerve regeneration and elastin formation within poly(glycerol sebacate)-based synthetic arterial grafts one-year post-implantation in a rat model.
Biomaterials
PUBLISHED: 08-29-2013
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The objective of this study was to evaluate the long-term performance of cell-free vascular grafts made from a fast-degrading elastic polymer. We fabricated small arterial grafts from microporous tubes of poly(glycerol sebacate) (PGS) reinforced with polycaprolactone (PCL) nanofibers on the outer surface. Grafts were interpositioned in rat abdominal aortas and characterized at 1 year post-implant. Grafts remodeled into "neoarteries" (regenerated arteries) with similar gross appearance to native rat aortas. Neoarteries mimic arterial tissue architecture with a confluent endothelium and media and adventita-like layers. Patent vessels (80%) showed no significant stenosis, dilation, or calcification. Neoarteries contain nerves and have the same amount of mature elastin as native arteries. Despite some differences in matrix organization, regenerated arteries had similar dynamic mechanical compliance to native arteries in vivo. Neoarteries responded to vasomotor agents, albeit with different magnitude than native aortas. These data suggest that an elastic vascular graft that resorbs quickly has potential to improve the performance of vascular grafts used in small arteries. This design may also promote constructive remodeling in other soft tissues.
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Thermal probe maskless lithography for 27.5 nm half-pitch Si technology.
Nano Lett.
PUBLISHED: 08-23-2013
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Thermal scanning probe lithography is used for creating lithographic patterns with 27.5 nm half-pitch line density in a 50 nm thick high carbon content organic resist on a Si substrate. The as-written patterns in the poly phthaladehyde thermal resist layer have a depth of 8 nm, and they are transformed into high-aspect ratio binary patterns in the high carbon content resist using a SiO2 hard-mask layer with a thickness of merely 4 nm and a sequence of selective reactive ion etching steps. Using this process, a line-edge roughness after transfer of 2.7 nm (3?) has been achieved. The patterns have also been transferred into 50 nm deep structures in the Si substrate with excellent conformal accuracy. The demonstrated process capabilities in terms of feature density and line-edge roughness are in accordance with todays requirements for maskless lithography, for example for the fabrication of extreme ultraviolet (EUV) masks.
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Monitoring vegetation dynamics and carbon stock density in miombo woodlands.
Carbon Balance Manag
PUBLISHED: 07-05-2013
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The United Nations Program for Reducing Emissions from Deforestation and Forest Degradation (REDD+) aims to reduce the 20% contribution to global emissions of greenhouse gases from the forest sector, offering a financial value of the carbon stored in forests as an incentive for local communities. The pre-requisite for the setup of a participatory REDD + Program is the monitoring, reporting and verification (MRV) of baseline carbon stocks and their changes over time. In this study, we investigated miombo woodlands dynamics in terms of composition, structure and biomass over a 4-year period (2005--2009), and the Carbon Stock Density (CSD) for the year 2009. The study was conducted in the Niassa National Reserve (NNR) in northern Mozambique, which is the 14th largest protected area in the world.
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The role of autologous fat grafting in secondary microsurgical breast reconstruction.
Ann Plast Surg
PUBLISHED: 06-22-2013
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Autologous breast reconstruction offers higher rates of patient satisfaction, but not all patients are ideal candidates, often due to inadequate volume of donor sites. Although autologous fat grafting is frequently used to augment volume and contour abnormalities in implant-based breast reconstruction, its clear utility in microsurgical breast reconstruction has yet to be defined. Here, we examined patients undergoing autologous microsurgical breast reconstruction with and without the adjunct of autologous fat grafting to clearly define utility and indications for use.
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Stacked profunda artery perforator flaps for unilateral breast reconstruction: a case report.
J Reconstr Microsurg
PUBLISHED: 06-19-2013
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A patient with a severe case of Poland syndrome presented with a painful capsular contracture from a previous implant-based breast reconstruction. She desired the implant to be removed and to proceed with autologous reconstruction, sizeable enough to match the volume of her contralateral breast. A paucity of abdominal donor tissue combined with the patients hesitancy to acquire an anterior scar excluded this location as a free tissue transfer option. As an alternative donor site, the profunda artery perforator (PAP) flap was chosen. Bilateral PAP flaps were harvested and stacked using anterograde and retrograde anastomoses to the internal mammary vessels. Enough volume was present to fill her chest wall concavity and provide adequate projection to achieve symmetry with her contralateral breast. Her donor sites healed well and remained inconspicuous, without generating difficulties sitting. In conclusion, stacked PAP flaps provide an excellent alternative to an abdominal donor site for achieving large volume unilateral breast reconstruction.
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Metabolic profiling of total homocysteine and related compounds in hyperhomocysteinemia: utility and limitations in diagnosing the cause of puzzling thrombophilia in a family.
JIMD Rep
PUBLISHED: 06-04-2013
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We describe a family illustrating the diagnostic difficulties occurring when pyridoxine-responsive cystathionine beta-synthase (CBS) deficiency presents with thrombotic disease without associated ocular, skeletal, or CNS abnormalities, a situation increasingly recognized. This family had several thromboembolic episodes in two generations with apparently inconstant elevations of plasma total homocysteine (tHcy). When taking (sometimes even low amounts) of pyridoxine, the affected family members had low-normal tHcy and normal values for cystathionine, methionine, and cysteine. Withdrawal of vitamin therapy was necessary before lower cystathionine, elevated methionine, and decreased cysteine became apparent, a pattern suggestive of CBS deficiency, leading to the finding that the affected members were each compound heterozygotes for CBS p.G307S and p.P49L. To assist more accurate diagnosis of adults presenting with thrombophilia found to have elevated tHcy, the patterns of methionine-related metabolites in CBS-deficient patients are compared in this article to those in patients with homocysteine remethylation defects, including inborn errors of folate or cobalamin metabolism, and untreated severe cobalamin or folate deficiency. Usually serum cystathionine is low in subjects with CBS deficiency and elevated in those with remethylation defects. S-Adenosylmethionine and S-adenosylhomocysteine are often markedly elevated in CBS deficiency when tHcy is above 100 umol/L. We conclude that there are likely other undiagnosed, highly B6-responsive adult patients with CBS deficiency, and that additional testing of cystathionine, total cysteine, methionine, and S-adenosylmethionine will be helpful in diagnosing them correctly and distinguishing CBS deficiency from remethylation defects.
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A novel approach to frontal sinus surgery: treatment algorithm revisited.
J Craniofac Surg
PUBLISHED: 05-30-2013
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Access to the frontal sinus remains a challenging problem for the craniofacial surgeon. A wide array of techniques including minimally invasive endoscopic approaches have been described. Here we present our technique using medical modeling to gain fast and safe access for multiple indications.
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Disruption of shmt1 impairs hippocampal neurogenesis and mnemonic function in mice.
J. Nutr.
PUBLISHED: 05-22-2013
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Impaired folate-mediated one-carbon metabolism (OCM) has emerged as a risk factor for several diseases associated with age-related cognitive decline, but the underlying mechanisms remain unknown and thus hinder the identification of subpopulations most vulnerable to OCM disruption. Here we investigated the role of serine hydroxymethyltransferase 1 (SHMT1), a folate-dependent enzyme regulating de novo thymidylate biosynthesis, in influencing neuronal and cognitive function in the adult mouse. We observed Shmt1 expression in the hippocampus, including the granule cell layer of the dentate gyrus (DG), and examined hippocampal neurogenesis and hippocampal-dependent fear conditioning in mice deficient for Shmt1. We used a 3 × 3 design in which adult male Shmt1(+/+), Shmt1(+/-), and Shmt1(-/-) mice were fed folic acid control (2 mg/kg), folic acid-deficient (0 mg/kg), or folic acid-supplemented (8 mg/kg) diets from weaning through the duration of the study. Proliferation within the DG was elevated by 70% in Shmt1(+/-) mice, yet the number of newborn mature neurons was reduced by 98% compared with that in Shmt1(+/+) mice. Concomitant with these alterations, Shmt1(+/-) mice showed a 45% reduction in mnemonic recall during trace fear conditioning. Dietary folate manipulations alone did not influence neural outcomes. Together, these data identify SHMT1 as one of the first enzymes within the OCM pathway to regulate neuronal and cognitive profiles and implicate impaired thymidylate biosynthesis in the etiology of folate-related neuropathogenesis.
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Venous coupler size in autologous breast reconstruction-does it matter?
Microsurgery
PUBLISHED: 05-01-2013
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Autologous microvascular breast reconstruction is an increasingly common procedure. While arterial anastomoses are traditionally being hand-sewn, venous anastomoses are often completed with a coupler device. The largest coupler size possible should be used, as determined by the smaller of either the donor or recipient vein. While its efficacy has been shown using 3.0-mm size and greater couplers, little is known about the consequences of using coupler sizes less than or equal to 2.5 mm. Methods: A retrospective chart review of patients undergoing autologous breast reconstruction was conducted at NYU Medical Center between November 2007 and November 2011. Flaps were divided into cohorts based on coupler size used: 2.0 mm, 2.5 mm, and 3.0 mm. Outcomes included incidence of arterial or venous insufficiency, hematoma, fat necrosis, partial flap loss, full flap loss, and need for future fat grafting. Results: One-hundred ninety-seven patients underwent 392 flaps during the study period. Patients were similar in age, type of flap, smoking status, and radiation history. Coupler size less than or equal to 2.0 mm was found to be a significant risk factor for venous insufficiency (P = 0.038), as well as for development of fat necrosis (P = 0.041) and future need for fat grafting (P = 0.050). In multivariate analysis, body mass index was found to be an independent risk factor for skin flap necrosis (P = 0.010) and full flap loss (P = 0.035). Conclusions: Complications were significantly increased in patients where couplers of 2.0 mm or less were used, therefore to be avoided whenever possible. When needed, more aggressive vessel exposure through rib harvest, the use of thoracodorsal vessels or hand-sewing the anastomosis should be considered in cases of internal mammary vein caliber of 2.0 mm or less.
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A comparison of physical and psychological features of responders and non-responders to cervical facet blocks in chronic whiplash.
BMC Musculoskelet Disord
PUBLISHED: 04-04-2013
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Cervical facet block (FB) procedures are often used as a diagnostic precursor to radiofrequency neurotomies (RFN) in the management of chronic whiplash associated disorders (WAD). Some individuals will respond to the FB procedures and others will not respond. Such responders and non-responders provided a sample of convenience to question whether there were differences in their physical and psychological features. This information may inform future predictive studies and ultimately the clinical selection of patients for FB procedures.
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Characterization of adipose-derived mesenchymal stem cell combinations for vascularized bone engineering.
Tissue Eng Part A
PUBLISHED: 03-18-2013
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Since bone repair and regeneration depend on vasculogenesis and osteogenesis, both of these processes are essential for successful vascularized bone engineering. Using adipose-derived stem cells (ASCs), we investigated temporal gene expression profiles, as well as bone nodule and endothelial tubule formation capacities, during osteogenic and vasculogenic ASC lineage commitment. Osteoprogenitor-enriched cell populations were found to express RUNX2, MSX2, SP7 (osterix), BGLAP (osteocalcin), SPARC (osteonectin), and SPP1 (osteopontin) in a temporally specific sequence. Irreversible commitment of ASCs to the osteogenic lineage occurred between days 6 and 9 of differentiation. Endothelioprogenitor-enriched cell populations expressed CD34, PECAM1 (CD31), ENG (CD105), FLT1 (Vascular endothelial growth factor [VEGFR1]), and KDR (VEGFR2). Capacity for microtubule formation was evident in as early as 3 days. Functional capacity was assessed in eight coculture combinations for both bone nodule and endothelial tubule formation, and the greatest expression of these end-differentiation phenotypes was observed in the combination of well-differentiated endothelial cells with less-differentiated osteoblastic cells. Taken together, our results demonstrate vascularized bone engineering utilizing ASCs is a promising enterprise, and that coculture strategies should focus on developing a more mature vascular network in combination with a less mature osteoblastic stromal cell.
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Identification of the lateral position of a virtual object based on echoes by humans.
Hear. Res.
PUBLISHED: 03-08-2013
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Echolocation offers a promising approach to improve the quality of life of people with blindness although little is known about the factors influencing object localisation using a searching strategy. In this paper, we describe a series of experiments using sighted and blind human listeners and a virtual auditory space technique to investigate the effects of the distance and orientation of a reflective object and the effect of stimulus bandwidth on ability to identify the right-versus-left position of the object, with bands of noise and durations from 10-400 ms. We found that performance reduced with increasing object distance. This was more rapid for object orientations where mirror-like reflection paths do not exist to both ears (i.e., most possible orientations); performance with these orientations was indistinguishable from chance at 1.8 m for even the best performing listeners in other conditions. Above-chance performance extended to larger distances when the echo was artificially presented in isolation, as might be achieved in practice by an assistive device. We also found that performance was primarily based on information above 2 kHz. Further research should extend these investigations to include other factors that are relevant to real-life echolocation.
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Grading lipoaspirate: is there an optimal density for fat grafting?
Plast. Reconstr. Surg.
PUBLISHED: 02-26-2013
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Clinical results of fat grafting have been unpredictable. In this article, the authors hypothesize that centrifugation creates "graded densities" of fat with varying characteristics that influence lipoaspirate persistence and quality.
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Profiles of cognitive functioning in a population-based sample of centenarians using factor mixture analysis.
Exp Aging Res
PUBLISHED: 02-21-2013
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BACKGROUND/STUDY CONTEXT: The goal of the study was to identify and characterize latent profiles (clusters) of cognitive functioning in centenarians and the psychometric properties of cognitive measures within them.
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Non-invasive assessment of elastic modulus of arterial constructs during cell culture using ultrasound elasticity imaging.
Ultrasound Med Biol
PUBLISHED: 02-10-2013
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Mechanical strength is a key design factor in tissue engineering of arteries. Most existing techniques assess the mechanical property of arterial constructs destructively, leading to sacrifice of a large number of animals. We propose an ultrasound-based non-invasive technique for the assessment of the mechanical strength of engineered arterial constructs. Tubular scaffolds made from a biodegradable elastomer and seeded with vascular fibroblasts and smooth muscle cells were cultured in a pulsatile-flow bioreactor. Scaffold distension was computed from ultrasound radiofrequency signals of the pulsating scaffold via 2-D phase-sensitive speckle tracking. Youngs modulus was then calculated by solving the inverse problem from the distension and the recorded pulse pressure. The stiffness thus computed from ultrasound correlated well with direct mechanical testing results. As the scaffolds matured in culture, ultrasound measurements indicated an increase in Youngs modulus, and histology confirmed the growth of cells and collagen fibrils in the constructs. The results indicate that ultrasound elastography can be used to assess and monitor non-invasively the mechanical properties of arterial constructs.
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Intraspecific relationships among wood density, leaf structural traits and environment in four co-occurring species of Nothofagus in New Zealand.
PLoS ONE
PUBLISHED: 02-07-2013
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Plant functional traits capture important variation in plant strategy and function. Recent literature has revealed that within-species variation in traits is greater than previously supposed. However, we still have a poor understanding of how intraspecific variation is coordinated among different traits, and how it is driven by environment. We quantified intraspecific variation in wood density and five leaf traits underpinning the leaf economics spectrum (leaf dry matter content, leaf mass per unit area, size, thickness and density) within and among four widespread Nothofagus tree species in southern New Zealand. We tested whether intraspecific relationships between wood density and leaf traits followed widely reported interspecific relationships, and whether variation in these traits was coordinated through shared responses to environmental factors. Sample sites varied widely in environmental variables, including soil fertility (25-900 mg kg(-1) total P), precipitation (668-4875 mm yr(-1)), temperature (5.2-12.4 °C mean annual temperature) and latitude (41-46 °S). Leaf traits were strongly correlated with one another within species, but not with wood density. There was some evidence for a positive relationship between wood density and leaf tissue density and dry matter content, but no evidence that leaf mass or leaf size were correlated with wood density; this highlights that leaf mass per unit area cannot be used as a surrogate for component leaf traits such as tissue density. Trait variation was predicted by environmental factors, but not consistently among different traits; e.g., only leaf thickness and leaf density responded to the same environmental cues as wood density. We conclude that although intraspecific variation in wood density and leaf traits is strongly driven by environmental factors, these responses are not strongly coordinated among functional traits even across co-occurring, closely-related plant species.
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Microsurgical breast reconstruction for nipple-sparing mastectomy.
Plast. Reconstr. Surg.
PUBLISHED: 01-30-2013
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Nipple-sparing mastectomy warrants thorough preoperative evaluation to effectively achieve risk reduction, high patient satisfaction, and improved aesthetic outcome. To the authors knowledge, this review represents the largest series of microsurgical breast reconstructions following nipple-sparing mastectomies.
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Adaptive feedback analysis and control of programmable stimuli for assessment of cerebrovascular function.
Med Biol Eng Comput
PUBLISHED: 01-22-2013
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The assessment of cerebrovascular regulatory mechanisms often requires flexibly controlled and precisely timed changes in arterial blood pressure (ABP) and/or inspired CO?. In this study, a new system for inducing variations in mean ABP was designed, implemented and tested using programmable sequences and programmable controls to induce pressure changes through bilateral thigh cuffs. The system is also integrated with a computer-controlled switch to select air or a CO?/air mixture to be provided via a face mask. Adaptive feedback control of a pressure generator was required to meet stringent specifications for fast changes, and accuracy in timing and pressure levels applied by the thigh cuffs. The implemented system consists of a PC-based signal analysis/control unit, a pressure control unit and a CO?/air control unit. Initial evaluations were carried out to compare the cuff pressure control performances between adaptive and non-adaptive control configurations. Results show that the adaptive control method can reduce the mean error in sustaining target pressure by 99.57 % and reduce the transient time in pressure increases by 45.21 %. The system has proven a highly effective tool in ongoing research on brain blood flow control.
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Development of selective comprehensive two-dimensional liquid chromatography with parallel first-dimension sampling and second-dimension separation--application to the quantitative analysis of furanocoumarins in apiaceous vegetables.
Anal Bioanal Chem
PUBLISHED: 01-16-2013
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Various implementations of two-dimensional high-performance liquid chromatography are increasingly being developed and applied to the analysis of complex materials, including those encountered in the analysis of foods, beverages, and nutraceuticals. Previously, we introduced the concept of selective comprehensive two-dimensional liquid chromatography (sLC × LC) as a hybrid between the more conventional, but extreme opposite sampling modes of heartcutting (LC-LC) and fully comprehensive (LC × LC) 2D separation. The sLC × LC approach breaks the link between first dimension ((1)D) sampling time and second dimension ((2)D) analysis time that is faced in LC × LC and allows very rapid (as low as 1 s) sampling of highly efficient (1)D separations, while at the same time allowing efficient (2)D separations on the timescale of tens of seconds. In this paper, we improve upon our previous sLC × LC work by demonstrating the ability to perform the processes of (1)D sampling and (2)D separation in parallel. This significantly improves the flexibility of the technique and allows targeted analysis of analytes that elute close together in time in the (1)D separation. To demonstrate the value of this added capability, we have developed a sLC × LC method using multi-wavelength ultraviolet absorbance detection for the quantitative analysis of six target furanocoumarin compounds in extracts of celery, parsley, and parsnips. We show that (2)D separations of (1)D effluent containing the target compounds of interest reveal the presence of unanticipated interferent peaks that would otherwise compromise the quantitative accuracy of the method. We also demonstrate the application of the chemometric method iterative key set factor analysis with alternating least-squares to sLC × LC to mathematically resolve target compounds that are only slightly separated chromatographically but not sufficiently resolved for accurate quantitation.
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Maternal diet supplemented with methyl-donors protects against atherosclerosis in F1 ApoE(-/-) mice.
PLoS ONE
PUBLISHED: 01-07-2013
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Atherosclerosis is an inflammatory condition of the arterial wall mediated by cells of both innate and adaptive immunity. T lymphocytes play an important role in orchestrating the pathogenic immune response involved in the acceleration of atherosclerosis. Previously, we have shown that a prenatal methyl-donor supplementation diet (MS), when fed to dams during pregnancy and lactation, decreased the T cell-mediated pro-inflammatory cytokine and chemokine response in F1 mice. In the current study, we report feeding Apolipoprotein E (ApoE(-/-)) deficient dams with the MS diet during pregnancy reduces atherosclerotic plaques in F1 mice that were fed high fat diet (HFD) after weaning. F1 mice from dams on the MS diet exhibited increased global T cell DNA methylation. T-cell chemokines and their receptors (in particular CCR2, CCR5, and CXCR3) play important roles in the inflammatory cell recruitment to vascular lesions. MS diet significantly reduced Ccr2 mRNA and protein expression in CD3+ T cells but not in CD11b+ monocytes in MS F1 mice relative to controls. F1 litter size, HFD consumption, body weight, and body fat were similar between control and MS diet groups. Moreover, serum thiol metabolite levels were similar between the two groups. However, MS diet is associated with significantly higher serum HDL and lower LDL+VLDL levels in comparison to F1 mice from dams on the control diet. Inflammatory cytokines (IL-17, TNF-?, IL-6) were also lower in MS F1 mice serum and conditioned media from T-cell culture. Altogether, these data suggest that the MS diet ameliorates development of atherosclerosis by inhibiting the T-cell Ccr2 expression, reducing inflammatory cytokines production and increasing serum HDL:LDL ratio.
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Cost-effective therapeutic hypothermia treatment device for hypoxic ischemic encephalopathy.
Med Devices (Auckl)
PUBLISHED: 01-03-2013
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Despite recent advances in neonatal care and monitoring, asphyxia globally accounts for 23% of the 4 million annual deaths of newborns, and leads to hypoxic-ischemic encephalopathy (HIE). Occurring in five of 1000 live-born infants globally and even more in developing countries, HIE is a serious problem that causes death in 25%-50% of affected neonates and neurological disability to at least 25% of survivors. In order to prevent the damage caused by HIE, our invention provides an effective whole-body cooling of the neonates by utilizing evaporation and an endothermic reaction. Our device is composed of basic electronics, clay pots, sand, and urea-based instant cold pack powder. A larger clay pot, lined with nearly 5 cm of sand, contains a smaller pot, where the neonate will be placed for therapeutic treatment. When the sand is mixed with instant cold pack urea powder and wetted with water, the device can extract heat from inside to outside and maintain the inner pot at 17°C for more than 24 hours with monitoring by LED lights and thermistors. Using a piglet model, we confirmed that our device fits the specific parameters of therapeutic hypothermia, lowering the body temperature to 33.5°C with a 1°C margin of error. After the therapeutic hypothermia treatment, warming is regulated by adjusting the amount of water added and the location of baby inside the device. Our invention uniquely limits the amount of electricity required to power and operate the device compared with current expensive and high-tech devices available in the United States. Our device costs a maximum of 40 dollars and is simple enough to be used in neonatal intensive care units in developing countries.
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Facile mutant identification via a single parental backcross method and application of whole genome sequencing based mapping pipelines.
Front Plant Sci
PUBLISHED: 01-01-2013
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Forward genetic screens have identified numerous genes involved in development and metabolism, and remain a cornerstone of biological research. However, to locate a causal mutation, the practice of crossing to a polymorphic background to generate a mapping population can be problematic if the mutant phenotype is difficult to recognize in the hybrid F2 progeny, or dependent on parental specific traits. Here in a screen for leaf hyponasty mutants, we have performed a single backcross of an Ethane Methyl Sulphonate (EMS) generated hyponastic mutant to its parent. Whole genome deep sequencing of a bulked homozygous F2 population and analysis via the Next Generation EMS mutation mapping pipeline (NGM) unambiguously determined the causal mutation to be a single nucleotide polymorphisim (SNP) residing in HASTY, a previously characterized gene involved in microRNA biogenesis. We have evaluated the feasibility of this backcross approach using three additional SNP mapping pipelines; SHOREmap, the GATK pipeline, and the samtools pipeline. Although there was variance in the identification of EMS SNPs, all returned the same outcome in clearly identifying the causal mutation in HASTY. The simplicity of performing a single parental backcross and genome sequencing a small pool of segregating mutants has great promise for identifying mutations that may be difficult to map using conventional approaches.
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Do assembly history effects attenuate from species to ecosystem properties? A field test with wood-inhabiting fungi.
Ecol. Lett.
PUBLISHED: 12-21-2011
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Assembly history, or the order of species arrival, can have wide-ranging effects on species, communities and ecosystems. However, it remains unclear whether assembly history primarily affects individual species, with effects attenuating at the level of communities and ecosystems or, alternatively, has consistent effect sizes across increasing levels of ecological organisation. We address this question using a field-based manipulation of assembly history of wood-inhabiting fungi. The largest effect sizes were observed for the frequency of some individual species, and mean effect sizes were lower for community metrics of fungi immigrating from the regional species pool. There was little evidence, however, of attenuation in effect sizes at the ecosystem level (carbon, nitrogen, decomposition) in comparison to the species or community level. These results indicate that assembly history can have strong effects on ecosystem properties even under natural levels of environmental variability.
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Long-term betaine therapy in a murine model of cystathionine beta-synthase deficient homocystinuria: decreased efficacy over time reveals a significant threshold effect between elevated homocysteine and thrombotic risk.
Mol. Genet. Metab.
PUBLISHED: 11-15-2011
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Classical homocystinuria (HCU) is caused by deficiency of cystathionine ?-synthase and is characterized by connective tissue disturbances, mental retardation and cardiovascular disease. Treatment for pyridoxine non-responsive HCU typically involves lowering homocysteine levels with a methionine-restricted diet and dietary supplementation with betaine. Compliance with the methionine-restricted diet is difficult and often poor. Investigating optimization of the efficacy of long-term betaine treatment in isolation from a methionine-restricted diet is precluded by ethical considerations regarding patient risk. The HO mouse model of HCU developed in our laboratory, exhibits constitutive expression of multiple pro-inflammatory cytokines and a hypercoagulative phenotype both of which respond to short-term betaine treatment. Investigation of the effects of long-term betaine treatment in the absence of methionine-restriction in HO HCU mice revealed that the ability of betaine treatment to lower homocysteine diminished significantly over time. Plasma metabolite analysis indicated that this effect was due at least in part, to reduced betaine-homocysteine S-methyltransferase (BHMT) mediated remethylation of homocysteine. Western blotting analysis revealed that BHMT protein levels are significantly repressed in untreated HCU mice but are significantly induced in the presence of betaine treatment. The observed increase in plasma homocysteine during prolonged betaine treatment was accompanied by a significant increase in the plasma levels of TNF-alpha and IL-1beta and reversion to a hypercoagulative phenotype. Our findings are consistent with a relatively sharp threshold effect between severely elevated plasma homocysteine and thrombotic risk in HCU and indicate that the HO mouse model can serve as a useful tool for both testing novel treatment strategies and examining the optimal timing and dosing of betaine treatment with a view toward optimizing clinical outcome.
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Nuclear localization of de novo thymidylate biosynthesis pathway is required to prevent uracil accumulation in DNA.
J. Biol. Chem.
PUBLISHED: 11-04-2011
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Uracil accumulates in DNA as a result of impaired folate-dependent de novo thymidylate biosynthesis, a pathway composed of the enzymes serine hydroxymethyltransferase (SHMT), thymidylate synthase (TYMS), and dihydrofolate reductase. In G1, this pathway is present in the cytoplasm and at S phase undergoes small ubiquitin-like modifier-dependent translocation to the nucleus. It is not known whether this pathway functions in the cytoplasm, nucleus, or both in vivo. SHMT1 generates 5,10-methylenetetrahydrofolate for de novo thymidylate biosynthesis, a limiting step in the pathway, but also tightly binds 5-methyltetrahydrofolate in the cytoplasm, a required cofactor for homocysteine remethylation. Overexpression of SHMT1 in cell cultures inhibits folate-dependent homocysteine remethylation and enhances thymidylate biosynthesis. In this study, the impact of increased Shmt1 expression on folate-mediated one-carbon metabolism was determined in mice that overexpress the Shmt1 cDNA (Shmt1tg+ mice). Compared with wild type mice, Shmt1tg+ mice exhibited elevated SHMT1 and TYMS protein levels in tissues and evidence for impaired homocysteine remethylation but surprisingly exhibited depressed levels of nuclear SHMT1 and TYMS, lower rates of nuclear de novo thymidylate biosynthesis, and a nearly 10-fold increase in uracil content in hepatic nuclear DNA when fed a folate- and choline-deficient diet. These results demonstrate that SHMT1 and TYMS localization to the nucleus is essential to prevent uracil accumulation in nuclear DNA and indicate that SHMT1-mediated nuclear de novo thymidylate synthesis is critical for maintaining DNA integrity.
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Two patients with hepatic mtDNA depletion syndromes and marked elevations of S-adenosylmethionine and methionine.
Mol. Genet. Metab.
PUBLISHED: 09-22-2011
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This paper reports studies of two patients proven by a variety of studies to have mitochondrial depletion syndromes due to mutations in either their MPV17 or DGUOK genes. Each was initially investigated metabolically because of plasma methionine concentrations as high as 15-21-fold above the upper limit of the reference range, then found also to have plasma levels of S-adenosylmethionine (AdoMet) 4.4-8.6-fold above the upper limit of the reference range. Assays of S-adenosylhomocysteine, total homocysteine, cystathionine, sarcosine, and other relevant metabolites and studies of their gene encoding glycine N-methyltransferase produced evidence suggesting they had none of the known causes of elevated methionine with or without elevated AdoMet. Patient 1 grew slowly and intermittently, but was cognitively normal. At age 7 years he was found to have hepatocellular carcinoma, underwent a liver transplant and died of progressive liver and renal failure at age almost 9 years. Patient 2 had a clinical course typical of DGUOK deficiency and died at age 8 ½ months. Although each patient had liver abnormalities, evidence is presented that such abnormalities are very unlikely to explain their elevations of AdoMet or the extent of their hypermethioninemias. A working hypothesis is presented suggesting that with mitochondrial depletion the normal usage of AdoMet by mitochondria is impaired, AdoMet accumulates in the cytoplasm of affected cells poor in glycine N-methyltransferase activity, the accumulated AdoMet causes methionine to accumulate by inhibiting activity of methionine adenosyltransferase II, and that both AdoMet and methionine consequently leak abnormally into the plasma.
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Understanding neuronal systems in movement control using Wiener/Volterra kernels: a dominant feature analysis.
J. Neurosci. Methods
PUBLISHED: 09-14-2011
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Although Volterra kernels have been extensively applied in modelling and analysis of biological systems, the relationship between the kernel characteristics and physiologically important features under study is still not revealed clearly. In this study, the link between Volterra kernels and dynamic response of neural systems which control animal movements was investigated and demonstrated using a dominant feature analysis. The new results show an effective but simplified method to use Volterra or Wiener kernels to understand and classify the neural systems which are responsible for the fundamental movements such as flexion and extension of animal limbs, and importantly demonstrate how the neuron pathways in locusts control joint activities of low and high frequency and perform fundamental joint movements such as position, velocity and acceleration. These results provide a useful insight into the nonlinear characteristics of neural systems in movement control and show a useful approach to the analysis of physiological systems using Volterra/Wiener kernels.
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Prevalence and predictors of anemia in a population-based study of octogenarians and centenarians in Georgia.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 09-05-2011
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Anemia has been associated with increased physical and financial costs and occurs more frequently in older individuals. Therefore, the primary objectives of this study were to examine the prevalence and possible predictors of anemia in the very old.
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Auditory spectral integration in the perception of static vowels.
J. Speech Lang. Hear. Res.
PUBLISHED: 08-23-2011
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To evaluate potential contributions of broadband spectral integration in the perception of static vowels. Specifically, can the auditory system infer formant frequency information from changes in the intensity weighting across harmonics when the formant itself is missing? Does this type of integration produce the same results in the lower (first formant [F1]) and higher (second formant [F2]) regions? Does the spacing between the spectral components affect a listeners ability to integrate the acoustic cues?
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Deep femoral artery perforator flap: a new perforator flap for breast reconstruction.
J Reconstr Microsurg
PUBLISHED: 08-09-2011
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We present the deep femoral artery perforator (DFAP) flap, a new perforator flap for breast reconstruction, with a detailed description of operative technique and four clinical examples. The DFAP flap allows harvest of tissue from the lower buttock and lateral thigh with similar territory to an in-the-crease inferior gluteal artery perforator (IGAP) flap but based on a different perforator. When present, the DFAP is the largest vessel supplying this territory and is often septocutaneous, facilitating dissection when compared with the IGAP flap. We used preoperative imaging with magnetic resonance angiography to assist in accurate flap planning which also permitted precise determination of perforator origin. In patients with either a contraindication to abdominal wall-based perforator flaps or weight distribution below the waist, the DFAP flap provides an alternative to the IGAP flap with an excellent pedicle and a favorable location on the lateral thigh.
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Progenitor cell mobilization enhances bone healing by means of improved neovascularization and osteogenesis.
Plast. Reconstr. Surg.
PUBLISHED: 07-27-2011
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Although bone repair is a relatively efficient process, a significant portion of patients fail to heal their fractures. Because adequate blood supply is essential to osteogenesis, the authors hypothesize that augmenting neovascularization by increasing the number of circulating progenitor cells will improve bony healing.
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Rapid Self-Assembly of Tubular Arterial Media Layer from Smooth Muscle Cells in Transient Fibrin Gel.
J Tissue Sci Eng
PUBLISHED: 06-26-2011
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BACKGROUND: Tissue engineered blood vessels could address the large clinical need for small caliber vascular grafts. Self-assembly approaches that employ transient scaffolds to form tissues from only cells and secreted matrix could form completely autologous vascular grafts that rapidly remodel and integrate with host tissue in vivo. The objective of this study was to develop a simple and rapid method to self-assemble vascular cells into vascular grafts. HYPOTHESIS: We hypothesized that entrapment in rapidly degrading fibrin gels could facilitate self-assembly of vascular smooth muscle cells into a tubular tissue comprised mainly of SMCs and secreted matrix. METHODS: Baboon SMCs were entrapped in fibrin around a silicone tube and cultured for 14 days without fibrinolysis inhibitor. Spontaneous delamination from the inner tube allowed for simple isolation of constructs with forceps. RESULTS: Engineered tissues are tubular, handleable, and highly cellular, with substantial collagen deposition. Fibrin is largely degraded within 14 days. Tensile elastic modulus of ring segments is 36.2 kPa and 1.60 MPa for the toe and heel regions of the stress-strain relation, respectively. CONCLUSION: Fibrin entrapment without fibrinolysis inhibitor can facilitate rapid self-assembly of SMCs into tubular tissues. Future work will focus on mechanical conditioning and co-culture with vascular endothelial cells to improve mechanical strength and impart antithrombogenicity.
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Size-specific tree mortality varies with neighbourhood crowding and disturbance in a Montane Nothofagus forest.
PLoS ONE
PUBLISHED: 06-03-2011
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Tree mortality is a fundamental process governing forest dynamics, but understanding tree mortality patterns is challenging because large, long-term datasets are required. Describing size-specific mortality patterns can be especially difficult, due to few trees in larger size classes. We used permanent plot data from Nothofagus solandri var. cliffortioides (mountain beech) forest on the eastern slopes of the Southern Alps, New Zealand, where the fates of trees on 250 plots of 0.04 ha were followed, to examine: (1) patterns of size-specific mortality over three consecutive periods spanning 30 years, each characterised by different disturbance, and (2) the strength and direction of neighbourhood crowding effects on size-specific mortality rates. We found that the size-specific mortality function was U-shaped over the 30-year period as well as within two shorter periods characterised by small-scale pinhole beetle and windthrow disturbance. During a third period, characterised by earthquake disturbance, tree mortality was less size dependent. Small trees (<20 cm in diameter) were more likely to die, in all three periods, if surrounded by a high basal area of larger neighbours, suggesting that size-asymmetric competition for light was a major cause of mortality. In contrast, large trees (? 20 cm in diameter) were more likely to die in the first period if they had few neighbours, indicating that positive crowding effects were sometimes important for survival of large trees. Overall our results suggest that temporal variability in size-specific mortality patterns, and positive interactions between large trees, may sometimes need to be incorporated into models of forest dynamics.
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Avascular necrosis of the capitate.
J Radiol Case Rep
PUBLISHED: 06-01-2011
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Avascular necrosis of the capitate is a rare entity. The most common reported etiology is trauma. We report a case of avascular necrosis of the capitate in a patient with chronic wrist pain that began after a single episode of remote trauma.
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The impact of primary melanoma thickness and microscopic tumor burden in sentinel lymph nodes on melanoma patient survival.
Ann. Surg. Oncol.
PUBLISHED: 05-31-2011
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The primary objectives of this work are to (1) quantitate tumor burden in sentinel lymph nodes (SLNs), and (2) assess the independent contributions of SLN tumor burden and primary melanoma thickness (PMT) with respect to progression-free survival (PFS) and overall survival (OS).
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Contrast-enhanced magnetic resonance angiography.
Clin Plast Surg
PUBLISHED: 05-31-2011
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With technological advances in magnetic resonance angiography (MRA), spatial resolution of 1-mm perforating vessels can reliably be visualized and accurately located in reference to patients anatomic landmarks without exposing patients to ionizing radiation or iodinated contrast, resulting in optimal perforator selection, improved flap design, and increased surgical efficiency. As their experience with MRA in breast reconstruction has increased, the authors have made changes to their MRA protocol that allow imaging of the vasculature in multiple donor sites (buttock, abdomen, and upper thigh) in one study. This article provides details of this experience with multiple donor site contrast-enhanced MRA.
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Characterization of airway device cuff volumes at simulated altitude.
Aviat Space Environ Med
PUBLISHED: 05-28-2011
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Cuff volume of an air-filled airway device varies inversely with ambient pressure at altitude. This may result in problems with ventilation, aspiration, and tissue ischemia in intubated patients transported by aircraft. We aimed to characterize cuff volume changes in airway devices as a function of altitude.
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Reducing the risk of shoulder dystocia and associated brachial plexus injury.
Obstet. Gynecol. Clin. North Am.
PUBLISHED: 05-18-2011
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Despite persisting controversy over shoulder dystocia prediction, prevention, and injury causation, the authors find considerable evidence in recent research in the field to recommend additional guidelines beyond the current American College of Obstetricians and Gynecologists and Royal College of Obstetricians and Gynecologists guidelines to improve clinical practice in managing patients at risk for experiencing shoulder dystocia. In this article, the authors offer health care providers information, practical direction, and advice on how to limit shoulder dystocia risk and, more importantly, to reduce adverse outcome risk.
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Serum methionine metabolites are risk factors for metastatic prostate cancer progression.
PLoS ONE
PUBLISHED: 05-16-2011
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Clinical decision for primary treatment for prostate cancer is dictated by variables with insufficient specificity. Early detection of prostate cancer likely to develop rapid recurrence could support neo-adjuvant therapeutics and adjuvant options prior to frank biochemical recurrence. This study compared markers in serum and urine of patients with rapidly recurrent prostate cancer to recurrence-free patients after radical prostatectomy. Based on previous identification of urinary sarcosine as a metastatic marker, we tested whether methionine metabolites in urine and serum could serve as pre-surgical markers for aggressive disease.
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Artificial niche combining elastomeric substrate and platelets guides vascular differentiation of bone marrow mononuclear cells.
Tissue Eng Part A
PUBLISHED: 05-12-2011
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Bone marrow-derived progenitor cells are promising cell sources for vascular tissue engineering. However, conventional bone marrow mesenchymal stem cell expansion and induction strategies require plating on tissue culture plastic, a stiff substrate that may itself influence cell differentiation. Direct scaffold seeding avoids plating on plastic; to the best of our knowledge, there is no report of any scaffold that induces the differentiation of bone marrow mononuclear cells (BMNCs) to vascular cells in vitro. In this study, we hypothesize that an elastomeric scaffold with adsorbed plasma proteins and platelets will induce differentiation of BMNCs to vascular cells and promote vascular tissue formation by combining soft tissue mechanical properties with platelet-mediated tissue repairing signals. To test our hypothesis, we directly seeded rat primary BMNCs in four types of scaffolds: poly(lactide-co-glycolide), elastomeric poly(glycerol sebacate) (PGS), platelet-poor plasma-coated PGS, and PGS coated by plasma supplemented with platelets. After 21 days of culture, osteochondral differentiation of cells in poly(lactide-co-glycolide) was detected, but most of the adhered cells on the surface of all PGS scaffolds expressed calponin-I and ?-smooth muscle actin, suggesting smooth muscle differentiation. Cells in PGS scaffolds also produced significant amount of collagen and elastin. Further, plasma coating improves seeding efficiency, and platelet increases proliferation, the number of differentiated cells, and extracellular matrix content. Thus, the artificial niche composed of platelets, plasma, and PGS is promising for artery tissue engineering using BMNCs.
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Severe shoulder dystocia with a small-for-gestationaI-age infant: a case report.
J Reprod Med
PUBLISHED: 05-06-2011
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Severe shoulder dystocia is disproportionately associated with large-for-gestational-age infants.
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Human fat grafting alleviates radiation skin damage in a murine model.
Plast. Reconstr. Surg.
PUBLISHED: 04-20-2011
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Autogenous fat grafting has been observed to alleviate the sequelae of chronic radiodermatitis. To date, no study has replicated this finding in an animal model.
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Dipyridamole monotherapy in schizophrenia: pilot of a novel treatment approach by modulation of purinergic signaling.
Psychopharmacology (Berl.)
PUBLISHED: 04-15-2011
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Emerging data indicate the neuromodulator adenosine may play a role in the therapeutics of schizophrenia. Adenosine A(2A) receptor stimulation exerts a functional antagonism at postsynaptic D(2) receptors. Data from animal models relevant to schizophrenia support a therapeutic effect of modulating adenosinergic transmission in the ventral striatum. One previous clinical trial showed superiority of adjunctive dipyridamole, an adenosine reuptake inhibitor, compared to placebo in ameliorating positive symptoms in schizophrenia patients.
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Selective sentinel lymph node dissection for melanoma: importance of harvesting nodes with lower radioactive counts without the need for blue dye.
Ann. Surg. Oncol.
PUBLISHED: 04-06-2011
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Determining how many sentinel lymph nodes (SLNs) should be removed for melanoma is important. The purpose of this study is to determine the frequency at which nodes that are less radioactive than the "hottest" node (which is negative) are positive for melanoma, how low of a radioactivity should warrant harvest, and if isosulfan blue is necessary.
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Constitutive induction of pro-inflammatory and chemotactic cytokines in cystathionine beta-synthase deficient homocystinuria.
Mol. Genet. Metab.
PUBLISHED: 03-29-2011
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Cystathionine beta-synthase (CBS) deficient homocystinuria (HCU) is an inherited metabolic defect that if untreated, typically results in cognitive impairment, connective tissue disturbances, atherosclerosis and thromboembolic disease. In recent years, chronic inappropriate expression of the inflammatory response has emerged as a major driving force of both thrombosis and atherosclerotic lesion development. We report here a characterization of the abnormalities in cytokine expression induced in both a mouse model of HCU and human subjects with the disease in the presence and absence of homocysteine lowering therapy. HCU mice exhibited highly significant induction of the pro-inflammatory cytokines Il-1alpha, Il-1beta and TNF-alpha. Similarly, in untreated/poorly compliant human subjects with HCU we observed constitutive induction of multiple pro-inflammatory cytokines (IL-1alpha, IL-6, TNF-alpha, Il-17 and IL-12(p70)) and chemotactic chemokines (fractalkine, MIP-1alpha and MIP-1beta) compared to normal controls. These HCU patients also exhibited significant induction of IL-9, TGF-alpha and G-CSF. The expression levels of anti-inflammatory cytokines were unaffected in both HCU mice and human subjects with the disease. In the human subjects, homocysteine lowering therapy was associated with either normalization or significant reduction of all of the pro-inflammatory cytokines and chemokines investigated. We conclude that HCU is a disease of chronic inflammation and that aberrant cytokine expression has the potential to contribute to multiple aspects of pathogenesis. Our findings indicate that anti-inflammatory strategies could serve as a useful adjuvant therapy for this disease.
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Investigation of interpolation techniques for the reconstruction of the first dimension of comprehensive two-dimensional liquid chromatography-diode array detector data.
Anal. Chim. Acta
PUBLISHED: 02-25-2011
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Simulated and experimental data were used to measure the effectiveness of common interpolation techniques during chromatographic alignment of comprehensive two-dimensional liquid chromatography-diode array detector (LC×LC-DAD) data. Interpolation was used to generate a sufficient number of data points in the sampled first chromatographic dimension to allow for alignment of retention times from different injections. Five different interpolation methods, linear interpolation followed by cross correlation, piecewise cubic Hermite interpolating polynomial, cubic spline, Fourier zero-filling, and Gaussian fitting, were investigated. The fully aligned chromatograms, in both the first and second chromatographic dimensions, were analyzed by parallel factor analysis to determine the relative area for each peak in each injection. A calibration curve was generated for the simulated data set. The standard error of prediction and percent relative standard deviation were calculated for the simulated peak for each technique. The Gaussian fitting interpolation technique resulted in the lowest standard error of prediction and average relative standard deviation for the simulated data. However, upon applying the interpolation techniques to the experimental data, most of the interpolation methods were not found to produce statistically different relative peak areas from each other. While most of the techniques were not statistically different, the performance was improved relative to the PARAFAC results obtained when analyzing the unaligned data.
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Shmt1 and de novo thymidylate biosynthesis underlie folate-responsive neural tube defects in mice.
Am. J. Clin. Nutr.
PUBLISHED: 02-23-2011
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Folic acid supplementation prevents the occurrence and recurrence of neural tube defects (NTDs), but the causal metabolic pathways underlying folic acid-responsive NTDs have not been established. Serine hydroxymethyltransferase (SHMT1) partitions folate-derived one-carbon units to thymidylate biosynthesis at the expense of cellular methylation, and therefore SHMT1-deficient mice are a model to investigate the metabolic origin of folate-associated pathologies.
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Gadofosveset trisodium-enhanced abdominal perforator MRA.
J Magn Reson Imaging
PUBLISHED: 02-18-2011
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To compare image quality including the number of perforators visualized, vessel contrast ratios, and vessel sharpness with blood pool and extracellular contrast agents in abdominal perforator flap magnetic resonance angiography (MRA).
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Evaluation of Lassa antiviral compound ST-193 in a guinea pig model.
Antiviral Res.
PUBLISHED: 02-18-2011
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Lassa virus (LASV), a member of the Arenaviridae family, causes a viral hemorrhagic fever endemic to West Africa, where as many as 300,000 infections occur per year. Presently, there are no FDA-approved LASV-specific vaccines or antiviral agents, although the antiviral drug ribavirin has shown some efficacy. A recently identified small-molecule inhibitor of arenavirus entry, ST-193, exhibits submicromolar antiviral activity in vitro. To determine the antiviral utility of ST-193 in vivo, we tested the efficacy of this compound in the LASV guinea pig model. Four groups of strain 13 guinea pigs were administered 25 or 80 mg/kg ST-193, 25 mg/kg of ribavirin, or the vehicle by the intraperitoneal (i.p.) route before infection with a lethal dose of LASV, strain Josiah, and continuing once daily for 14 days. Control animals exhibited severe disease, becoming moribund between days 10 and 15 postinfection. ST-193-treated animals exhibited fewer signs of disease and enhanced survival when compared to the ribavirin or vehicle groups. Body temperatures in all groups were elevated by day 9, but returned to normal by day 19 postinfection in the majority of ST-193-treated animals. ST-193 treatment mediated a 2-3-log reduction in viremia relative to vehicle-treated controls. The overall survival rate for the ST-193-treated guinea pigs was 62.5% (10/16) compared with 0% in the ribavirin (0/8) and vehicle (0/7) groups. These data suggest that ST-193 may serve as an improved candidate for the treatment of Lassa fever.
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Perforator flap breast reconstruction after unsatisfactory implant reconstruction.
Ann Plast Surg
PUBLISHED: 02-09-2011
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In 2009, 86,424 breast reconstructions were performed in the United States, with 76% being implant-based procedures. Capsular contracture and infection are the 2 most cited indications for implant explantation, resulting in a reconstruction failure. However, several patients are dissatisfied with implant reconstruction even without the aforementioned complications. We hypothesize that microvascular autologous tissue transfer with perforator free-flap breast reconstruction provides an excellent salvage modality in the face of an unsatisfactory implant reconstruction, resulting in an improved cosmetic and functional outcome, with low risk of complications. We retrospectively reviewed the charts of patients in the senior authors practice who underwent perforator flap breast reconstruction between the years 1998 through 2008, and identified all patients who had prior implant reconstruction. Indications for implant explantation, medical history, operative procedure, and postoperative complications were reviewed. During the study period, 1846 perforator flaps were performed. We found 191 patients who underwent autologous breast reconstruction after implant reconstruction with a total of 284 flaps (15.4%). The most frequent patient complaint was unnatural appearance and feel of the implants (Baker I or Baker II), and the majority of patients had not undergone radiation. Most patients were reconstructed using abdominal flaps with 164 deep inferior epigastric perforators, 50 superior gluteal artery perforators, 30 superficial inferior epigastric arteries, 35 inferior gluteal artery perforators, and 5 transverse upper gracilis. The total complication rate was 7.4%, with most complications related to wound healing at the donor site. There were 3 flap losses (1%), all of which were later successfully reconstructed with another perforator flap. Implant failures are traditionally thought to be in patients with Baker grade III/IV capsular contractures and in patients status post radiation therapy. However, in our study, the majority of patients seeking perforator flap reconstruction after implant reconstruction complained of an unnatural feel and appearance of their breasts, and did not have a severe capsular contracture deformity (Baker III/IV), nor had they undergone radiation. This suggests that implant reconstruction can lead to patient dissatisfaction severe enough to warrant removal even with Baker I/II results, and not in the setting of postradiation changes.
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A novel mouse model of cutaneous radiation injury.
Plast. Reconstr. Surg.
PUBLISHED: 02-03-2011
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Radiation therapy is a cornerstone of oncologic treatment. Skin tolerance is often the limiting factor in radiotherapy. To study these issues and create modalities for intervention, the authors developed a novel murine model of cutaneous radiation injury.
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Introducing the septocutaneous gluteal artery perforator flap: a simplified approach to microsurgical breast reconstruction.
Plast. Reconstr. Surg.
PUBLISHED: 02-03-2011
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Consistent septocutaneous perforators exist between the gluteus maximus and medius muscles. The existence of these septocutaneous perforators obviates the need for any intramuscular dissection when elevating a gluteal artery perforator flap. In this study, the authors present their experience with the septocutaneous gluteal artery perforator (sc-GAP) flap for microsurgical breast reconstruction.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.