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1.
Cell ; 145(4): 571-83, 2011 May 13.
Article in English | MEDLINE | ID: mdl-21565614

ABSTRACT

The molecular basis for p53-mediated tumor suppression remains unclear. Here, to elucidate mechanisms of p53 tumor suppression, we use knockin mice expressing an allelic series of p53 transcriptional activation mutants. Microarray analysis reveals that one mutant, p53(25,26), is severely compromised for transactivation of most p53 target genes, and, moreover, p53(25,26) cannot induce G(1)-arrest or apoptosis in response to acute DNA damage. Surprisingly, p53(25,26) retains robust activity in senescence and tumor suppression, indicating that efficient transactivation of the majority of known p53 targets is dispensable for these pathways. In contrast, the transactivation-dead p53(25,26,53,54) mutant cannot induce senescence or inhibit tumorigenesis, like p53 nullizygosity. Thus, p53 transactivation is essential for tumor suppression but, intriguingly, in association with a small set of novel p53 target genes. Together, our studies distinguish the p53 transcriptional programs involved in acute DNA-damage responses and tumor suppression-a critical goal for designing therapeutics that block p53-dependent side effects of chemotherapy without compromising p53 tumor suppression.


Subject(s)
DNA Repair , Tumor Suppressor Protein p53/metabolism , Animals , Apoptosis , Cell Cycle , Cellular Senescence , DNA Damage , Gene Knock-In Techniques , Humans , Mice , Mutation , Neoplasms/metabolism , Protein Structure, Tertiary , Transcriptional Activation , Tumor Suppressor Protein p53/chemistry , Tumor Suppressor Protein p53/genetics
2.
Anal Chem ; 95(4): 2253-2259, 2023 Jan 31.
Article in English | MEDLINE | ID: mdl-36638820

ABSTRACT

Double spike (DS) method has been extensively used in determining stable isotope ratios of many elements. However, challenges remain in obtaining high-precision isotope data for ultra-trace elements owing to the limitations of instrumental signal-to-noise ratios and the systematics of precision of DS-based measurements. Here, the DS-standard addition (SA) (DSSA) technique is proposed to improve measurements of isotope compositions of ultra-trace elements in natural samples. According to the U-shaped relationship between DS measurement uncertainty and the spike/sample ratio, theoretical equations and an error propagation model (EPM) were constructed comprehensively. In our method, a spiked secondary standard solution with a high, precisely known spike/sample ratio is mixed with samples such that the mixtures have spike/sample ratios within the optimal range. The abundances of the samples relative to the added standards (sample fraction; fspl) and the samples' isotope ratios can then be obtained exactly using a standard DS data reduction routine and the isotope binary mixing model. The accuracy and precision of the DSSA approach were verified by measurements of cadmium and molybdenum isotopes at as low as 5 ng levels. Compared with traditional DS measurements, the sample size for isotope analysis is reduced to 1/6-1/5 of the original with no loss of measurement precision. The optimal mixing range fspl = 0.15-0.5 is recommended. The DSSA method can be extended to isotope measurement of more than 33 elements where the DS method is applicable, especially for the ultra-trace elements such as platinum group and rare earth element isotopes.

3.
Anal Chem ; 93(20): 7449-7455, 2021 05 25.
Article in English | MEDLINE | ID: mdl-33974413

ABSTRACT

Stable isotope ratios are widely used to solve environmental, geological, medical, and forensic problems. The double spike technique is considered to be one of the most robust and efficient methods to correct for instrumental mass bias and isotopic fractionation that may occur during sample preparation. However, various hidden errors can arise from data processing and have been largely overlooked in previous studies. Several of these hidden errors were investigated in this work using measurement and synthetic data. Double spike inversion of chromium isotope raw data from 1116 natural samples demonstrated that averaging raw isotope ratios before double spike inversion can add significant errors to inverted isotope values, and such errors can be 1.5 times larger than the true analytical precision. Synthetic data were used to investigate the errors on inverted Cr isotope data caused by spike:analyte ratio and Fe-Ti-V interferences, and the following threshold values are recommended to minimize such errors: 54Crspike/52Crsample ratio greater than 0.5, 56Fe/52Cr less than 0.2, 49Ti/52Cr less than 0.04, and 51V/52Cr less than 1. Sample preparation can potentially lead to large errors in inverted Cr isotope data if preparation-induced isotope fractionation deviates from the exponential law used in the double spike inversion, but such errors can be minimized by achieving >70% Cr yield. Our findings provide important insights for the double spike inversion procedure and assessing the reliability of inverted isotope data for not only the chromium isotope system but also other elements commonly analyzed using the double spike technique.


Subject(s)
Chemical Fractionation , Isotopes , Chromium , Chromium Isotopes , Reproducibility of Results
4.
Anal Chem ; 92(1): 1463-1469, 2020 01 07.
Article in English | MEDLINE | ID: mdl-31766840

ABSTRACT

High-sensitivity and high-precision (2 SD ≤ 0.06‰) measurement of chromium (Cr) isotopes at the 10 ng level was successfully carried out using double spike multiple-collector inductively couple plasma mass spectrometry (MC-ICP-MS). To enhance the signal sensitivity and stability, the Aridus II desolvating nebulizer system was improved by placing its waste gas trap bottle in an ice chamber (5 °C cold trap). This setup, beyond Cr isotope analysis, can be applied to most heavy metal isotope measurements. The sensitivity of the 52Cr signal is ≥300 V mg-1 L (with a 1011Ω amplifier and a 110 µL min-1 uptake rate), an enhancement of ≥1.5 times compared to the Aridus II without the cold trap. In addition, the relative standard deviation of the 52Cr signal varied ≤4% over 8 h, demonstrating high stability. The δ53Cr values of common geological reference materials determined using 10 ng of Cr are in excellent agreement with results measured at 25 ng and 50 ng and are consistent with previous determinations, validating the accurate and precise Cr isotope ratio measurements. An empirical method is proposed to correct for the residual (after subtraction) effect of Fe interference on δ53Cr determination. This method relies on a linear relationship between the [Fe]/[Cr] and δ53Cr shift within one analytical session. Finally, we report the δ53Cr values of 19 new reference materials, ranging from -0.44‰ to 0.49‰. Among them, GSS-7 (-0.44 ± 0.02‰, 2 SD, n = 5), GSS-4 (0.48 ± 0.02‰, 2 SD, n = 5), and GSD-10 (0.49 ± 0.05‰, 2 SD, n = 5) can be used as candidate reference materials for interlaboratory comparisons to complement existing ones that are mostly isotopically unfractionated from the bulk silicate earth.

5.
Environ Sci Technol ; 54(4): 2295-2303, 2020 02 18.
Article in English | MEDLINE | ID: mdl-31909614

ABSTRACT

U isotope fractionation may serve as an accurate proxy for U(VI) reduction in both modern and ancient environments, if the systematic controls on the magnitude of fractionation (ε) are known. We model the effect of U(VI) reduction kinetics on U isotopic fractionation during U(VI) reduction by a novel Shewanella isolate, Shewanella sp. (NR), in batch incubations. The measured ε values range from 0.96 ± 0.16 to 0.36 ± 0.07‰ and are strongly dependent on the U(VI) reduction rate. The ε decreases with increasing reduction rate constants normalized by cell density and initial U(VI). Reactive transport simulations suggest that the rate dependence of ε is due to a two-step process, where diffusive transport of U(VI) from the bulk solution across a boundary layer is followed by enzymatic reduction. Our results imply that the spatial decoupling of bulk U(VI) solution and enzymatic reduction should be taken into account for interpreting U isotope data from the environment.


Subject(s)
Chemical Fractionation , Chromium , Isotopes , Kinetics , Oxidation-Reduction
6.
Nature ; 514(7521): 228-32, 2014 Oct 09.
Article in English | MEDLINE | ID: mdl-25119037

ABSTRACT

CHARGE syndrome is a multiple anomaly disorder in which patients present with a variety of phenotypes, including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genitourinary hypoplasia and ear abnormalities. Despite 70-90% of CHARGE syndrome cases resulting from mutations in the gene CHD7, which encodes an ATP-dependent chromatin remodeller, the pathways underlying the diverse phenotypes remain poorly understood. Surprisingly, our studies of a knock-in mutant mouse strain that expresses a stabilized and transcriptionally dead variant of the tumour-suppressor protein p53 (p53(25,26,53,54)), along with a wild-type allele of p53 (also known as Trp53), revealed late-gestational embryonic lethality associated with a host of phenotypes that are characteristic of CHARGE syndrome, including coloboma, inner and outer ear malformations, heart outflow tract defects and craniofacial defects. We found that the p53(25,26,53,54) mutant protein stabilized and hyperactivated wild-type p53, which then inappropriately induced its target genes and triggered cell-cycle arrest or apoptosis during development. Importantly, these phenotypes were only observed with a wild-type p53 allele, as p53(25,26,53,54)(/-) embryos were fully viable. Furthermore, we found that CHD7 can bind to the p53 promoter, thereby negatively regulating p53 expression, and that CHD7 loss in mouse neural crest cells or samples from patients with CHARGE syndrome results in p53 activation. Strikingly, we found that p53 heterozygosity partially rescued the phenotypes in Chd7-null mouse embryos, demonstrating that p53 contributes to the phenotypes that result from CHD7 loss. Thus, inappropriate p53 activation during development can promote CHARGE phenotypes, supporting the idea that p53 has a critical role in developmental syndromes and providing important insight into the mechanisms underlying CHARGE syndrome.


Subject(s)
Abnormalities, Multiple/metabolism , CHARGE Syndrome/genetics , CHARGE Syndrome/metabolism , Phenotype , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Abnormalities, Multiple/genetics , Alleles , Animals , Apoptosis/genetics , Cell Cycle Checkpoints/genetics , Craniofacial Abnormalities/genetics , Craniofacial Abnormalities/metabolism , DNA-Binding Proteins/deficiency , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Ear/abnormalities , Embryo, Mammalian/abnormalities , Embryo, Mammalian/metabolism , Female , Fibroblasts , Gene Deletion , Heterozygote , Humans , Male , Mice , Mutant Proteins/metabolism , Promoter Regions, Genetic/genetics
7.
Environ Sci Technol ; 52(6): 3422-3430, 2018 03 20.
Article in English | MEDLINE | ID: mdl-29464949

ABSTRACT

Biostimulation to induce reduction of soluble U(VI) to relatively immobile U(IV) is an effective strategy for decreasing aqueous U(VI) concentrations in contaminated groundwater systems. If oxidation of U(IV) occurs following the biostimulation phase, U(VI) concentrations increase, challenging the long-term effectiveness of this technique. However, detecting U(IV) oxidation through dissolved U concentrations alone can prove difficult in locations with few groundwater wells to track the addition of U to a mass of groundwater. We propose the 238U/235U ratio of aqueous U as an independent, reliable tracer of U(IV) remobilization via oxidation or mobilization of colloids. Reduction of U(VI) produces 238U-enriched U(IV), whereas remobilization of solid U(IV) should not induce isotopic fractionation. The incorporation of remobilized U(IV) with a high 238U/235U ratio into the aqueous U(VI) pool produces an increase in 238U/235U of aqueous U(VI). During several injections of nitrate to induce U(IV) oxidation, 238U/235U consistently increased, suggesting 238U/235U is broadly applicable for detecting mobilization of U(IV).


Subject(s)
Groundwater , Uranium , Water Pollutants, Radioactive , Biodegradation, Environmental , Nitrates , Oxidation-Reduction
8.
Am J Emerg Med ; 36(10): 1928.e5-1928.e7, 2018 10.
Article in English | MEDLINE | ID: mdl-29983216

ABSTRACT

Locked-in syndrome (LIS) is an exceedingly rare condition that has been described as a fate worse than death. Unfortunately, exam findings can be subtle and imaging is poorly sensitive, often leading to a delay in diagnosis. We present a case of a 70-year-old female who presented to our emergency department after developing respiratory distress followed by sudden unresponsiveness. She was diagnosed with LIS and had an immediate and remarkable improvement after administration of tissue plasminogen activator (TPA). Patients presenting with sudden onset altered mental status require a very careful physical exam, even if deemed comatose, and should be considered for emergent imaging for stroke. Fortunately, our patient recovered well and was discharged home in good condition.


Subject(s)
Fibrinolytic Agents/administration & dosage , Quadriplegia/drug therapy , Recovery of Function/drug effects , Tissue Plasminogen Activator/administration & dosage , Aged , Critical Care , Female , Humans , Quadriplegia/diagnosis , Quadriplegia/physiopathology , Recovery of Function/physiology , Tomography, X-Ray Computed , Treatment Outcome
9.
Qual Life Res ; 26(6): 1551-1559, 2017 06.
Article in English | MEDLINE | ID: mdl-28188563

ABSTRACT

BACKGROUND: Currently, 2.5 million orphaned children are living in Kenya and 56 million orphaned children are living across sub-Saharan Africa. No empirical research has investigated meaningfulness of life among this population, and few studies provide perspectives on the life-course consequences of losing a parent during childhood. METHODS: In this study, we assess life meaningfulness in cross section of Kenyan women (n = 1974) in a semi-rural area of the country (Meru County) collected during June 2015. We used two sets of mediation analyses to assess (1) whether meaningfulness of life was lower among women who reported a parental death during their childhood, and how this association was mediated by social support, family functioning, school completion and HIV+ status of household, and (2) the extent to which lower subjective overall health among women who experienced orphanhood during childhood was mediated by less meaningfulness of life. RESULTS: Women who experienced a parental death during childhood reported significantly less meaningful lives as adults. Lower social support and family functioning explained approximately 40% of the disparity. Women who experienced a parental death during childhood also had significantly worse subjective overall health, 18% of which was explained by lower meaningfulness of life. CONCLUSIONS: Further study on life meaningfulness and family capital in the context of the orphan crisis in sub-Saharan Africa is warranted, and required to promote equity across the lifespan. Policy efforts to support orphans and vulnerable children should target strengthening support networks and family functioning to optimize self-reported health outcomes.


Subject(s)
Child, Orphaned/psychology , Delivery of Health Care/standards , Meaningful Use/standards , Quality of Life/psychology , Adolescent , Adult , Child , Cross-Sectional Studies , Female , Humans , Kenya , Social Support , Surveys and Questionnaires
10.
J Bacteriol ; 198(19): 2608-18, 2016 10 01.
Article in English | MEDLINE | ID: mdl-27021563

ABSTRACT

UNLABELLED: The ecological and evolutionary forces that promote and maintain diversity in biofilms are not well understood. To quantify these forces, three Pseudomonas aeruginosa populations were experimentally evolved from strain PA14 in a daily cycle of attachment, assembly, and dispersal for 600 generations. Each biofilm population evolved diverse colony morphologies and mutator genotypes defective in DNA mismatch repair. This diversity enhanced population fitness and biofilm output, owing partly to rare, early colonizing mutants that enhanced attachment of others. Evolved mutants exhibited various levels of the intracellular signal cyclic-di-GMP, which associated with their timing of adherence. Manipulating cyclic-di-GMP levels within individual mutants revealed a network of interactions in the population that depended on various attachment strategies related to this signal. Diversification in biofilms may therefore arise and be reinforced by initial colonists that enable community assembly. IMPORTANCE: How biofilm diversity assembles, evolves, and contributes to community function is largely unknown. This presents a major challenge for understanding evolution during chronic infections and during the growth of all surface-associated microbes. We used experimental evolution to probe these dynamics and found that diversity, partly related to altered cyclic-di-GMP levels, arose and persisted due to the emergence of ecological interdependencies related to attachment patterns. Clonal isolates failed to capture population attributes, which points to the need to account for diversity in infections. More broadly, this study offers an experimental framework for linking phenotypic variation to distinct ecological strategies in biofilms and for studying eco-evolutionary interactions.


Subject(s)
Biofilms/growth & development , Cyclic GMP/analogs & derivatives , Pseudomonas aeruginosa/physiology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Bacteriological Techniques , Cyclic GMP/metabolism , Directed Molecular Evolution , Ecosystem , Gene Expression Regulation, Bacterial/physiology , Mutation , Signal Transduction
11.
Environ Sci Technol ; 50(20): 10833-10842, 2016 Oct 18.
Article in English | MEDLINE | ID: mdl-27547844

ABSTRACT

One of the major ecological concerns associated with the in situ recovery (ISR) of uranium (U) is the environmental release of soluble, toxic selenium (Se) oxyanions generated by mining. Post-mining natural attenuation by the residual reductants in the ore body and reduced down-gradient sediments should mitigate the risk of Se contamination in groundwater. In this work, we investigate the Se concentrations and Se isotope systematics of groundwater and of U ore bearing sediments from an ISR site at Rosita, TX, USA. Our results show that selenate (Se(VI)) is the dominant Se species in Rosita groundwater, and while several up-gradient wells have elevated Se(VI), the majority of the ore zone and down-gradient wells have little or no Se oxyanions. In addition, the δ82SeVI of Rosita groundwater is generally elevated relative to the U ore up to +6.14‰, with the most enriched values observed in the ore-zone wells. Increasing δ82Se with decreasing Se(VI) conforms to a Rayleigh type distillation model with an ε of -2.25‰ ± 0.61‰, suggesting natural Se(VI) reduction occurring along the hydraulic gradient at the Rosita ISR site. Furthermore, our results show that Se isotopes are excellent sensors for detecting and monitoring post-mining natural attenuation of Se oxyanions at ISR sites.

12.
Environ Sci Technol ; 49(16): 9690-8, 2015 Aug 18.
Article in English | MEDLINE | ID: mdl-26177307

ABSTRACT

Selenium poisoning is a significant health problem in parts of Punjab, India, which is an area of intense agricultural productivity. To determine the complex soil dynamics that control distribution of Se in this area, we measured concentrations and δ(82/76)Se of bulk Se and individual Se pools in four soil profiles. This was compared against δ(82/76)Se of crops and groundwater used for irrigation. The isotopic composition of bulk Se and component Se pools reveal spatial heterogeneity. The bulk δ(82/76)Se show progressively lower values with increasing soil depth indicating the preferential migration of isotopically lighter Se downward through the soil profile. The δ(82/76)Se of water-soluble Se is isotopically heavier than δ(82/76)Se of adsorbed Se, suggesting Se isotope fractionation by reduction prior to scavenging by reactive minerals in the soil. The organically bound Se is isotopically lighter than water-soluble Se and correlates with the C/N ratio at different soil depths. Thus, Se immobilization by redox cycling controls the biogeochemical Se cycle in the soil. Se isotope ratios help to trace biochemical processes of Se in agricultural seleniferous soils and provide an important assessment for better soil management mitigating Se concentrations of ecotoxicological levels.


Subject(s)
Isotopes/analysis , Selenium/analysis , Soil/chemistry , Crops, Agricultural/chemistry , Environmental Monitoring/methods , India , Isotopes/metabolism , Selenium/metabolism , Selenium Compounds/metabolism , Solubility , Water/chemistry
13.
Proc Natl Acad Sci U S A ; 108(41): 17123-8, 2011 Oct 11.
Article in English | MEDLINE | ID: mdl-21969549

ABSTRACT

Over half of all human cancers, of a wide variety of types, sustain mutations in the p53 tumor suppressor gene. Although p53 limits tumorigenesis through the induction of apoptosis or cell cycle arrest, its molecular mechanism of action in tumor suppression has been elusive. The best-characterized p53 activity in vitro is as a transcriptional activator, but the identification of numerous additional p53 biochemical activities in vitro has made it unclear which mechanism accounts for tumor suppression. Here, we assess the importance of transcriptional activation for p53 tumor suppression function in vivo in several tissues, using a knock-in mouse strain expressing a p53 mutant compromised for transcriptional activation, p53(25,26). p53(25,26) is severely impaired for the transactivation of numerous classical p53 target genes, including p21, Noxa, and Puma, but it retains the ability to activate a small subset of p53 target genes, including Bax. Surprisingly, p53(25,26) can nonetheless suppress tumor growth in cancers derived from the epithelial, mesenchymal, central nervous system, and lymphoid lineages. Therefore, full transactivation of most p53 target genes is dispensable for p53 tumor suppressor function in a range of tissue types. In contrast, a transcriptional activation mutant that is completely defective for transactivation, p53(25,26,53,54), fails to suppress tumor development. These findings demonstrate that transcriptional activation is indeed broadly critical for p53 tumor suppressor function, although this requirement reflects the limited transcriptional activity observed with p53(25,26) rather than robust transactivation of a full complement of p53 target genes.


Subject(s)
Genes, p53 , Neoplasms/genetics , Neoplasms/prevention & control , Animals , Cell Lineage/genetics , Gene Knock-In Techniques , Humans , Lymphoma, B-Cell/genetics , Lymphoma, B-Cell/prevention & control , Medulloblastoma/genetics , Medulloblastoma/prevention & control , Mice , Mice, Knockout , Mice, Transgenic , Mutation , Transcriptional Activation
14.
Nat Genet ; 37(2): 145-52, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15654339

ABSTRACT

The role of transcriptional activation in p53 function is highly controversial. To define this role in vivo, we generated a Trp53 knock-in construct encoding a protein carrying mutations of two residues that are crucial for transactivation (L25Q,W26S). Here we show that these mutations have selective effects on the biological functions of p53. Although its ability to activate various p53 target genes is largely compromised, the p53(QS) protein retains the ability to transactivate the gene Bax. The ability of the p53(QS) mutant protein to elicit a DNA damage-induced G1 cell cycle-arrest response is also partially impaired. p53(QS) has selective defects in its ability to induce apoptosis: it is completely unable to activate apoptosis in response to DNA damage, is partially unable to do so when subjected to serum deprivation and retains substantial apoptotic activity upon exposure to hypoxia. These findings suggest that p53 acts through distinct, stimulus-specific pathways to induce apoptosis. The importance of the biological activity of p53(QS) in vivo is underscored by our finding that expression of p53(QS), which cannot bind mdm2, induces embryonic lethality. Taken together, these results suggest that p53 has different mechanisms of action depending on specific contextual cues, which may help to clarify the function of p53 in preventing cancer.


Subject(s)
Apoptosis/genetics , Genes, p53 , Mutation , Trans-Activators/genetics , Transcriptional Activation , Animals , Cell Cycle/genetics , DNA Damage , Embryo, Mammalian , Gene Expression Regulation, Neoplastic , Mice , Mice, Transgenic , Nuclear Proteins , Proto-Oncogene Proteins , Proto-Oncogene Proteins c-bcl-2 , Proto-Oncogene Proteins c-mdm2 , Transfection , bcl-2-Associated X Protein
15.
Imaging Sci Dent ; 54(2): 121-127, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38948184

ABSTRACT

Purpose: Preoperative identification of the intraosseous posterior superior alveolar artery (PSAA) is critical when planning sinus surgery. This study was conducted to determine the distance between the cementoenamel junction and the PSAA, as well as to identify factors influencing the detection of the PSAA on cone-beam computed tomography (CBCT). Materials and Methods: In total, 254 CBCT scans of maxillary sinuses, acquired with 2 different scanners, were examined to identify the PSAA. The distance from the cementoenamel junction (CEJ) to the PSAA was recorded at each maxillary posterior tooth position. Binomial logistic regression and multiple linear regression were employed to evaluate the effects of scanner type, CBCT parameters, sex, and age on PSAA detection and CEJ-PSAA distance, respectively. P-values less than 0.05 were considered to indicate statistical significance. Results: The mean CEJ-PSAA distances at the second molar, first molar, second premolar, and first premolar positions were 17.0±4.0 mm, 21.8±4.1 mm, 19.5±4.7 mm, and 19.9±4.9 mm for scanner 1, respectively, and 17.3±3.5 mm, 16.9±4.3 mm, 18.5±4.1 mm, and 18.4±4.3 mm for scanner 2. No independent variable significantly influenced PSAA detection. However, tooth position (b=-0.67, P<0.05) and scanner type (b=-1.3, P<0.05) were significant predictors of CEJ-PSAA distance. Conclusion: CBCT-based estimates of CEJ-PSAA distance were comparable to those obtained in previous studies involving cadavers, CT, and CBCT. The type of CBCT scanner may slightly influence this measurement. No independent variable significantly impacted PSAA detection.

16.
Clin Exp Dent Res ; 10(1): e849, 2024 02.
Article in English | MEDLINE | ID: mdl-38345517

ABSTRACT

OBJECTIVES: In periodontology, it is widely recognized that evidence characterizing the incidence and effect of treatment complications is lacking. The objective of this study was to assess the influence of operator-, procedure-, patient-, and site-associated factors on intraoperative and postoperative complication occurrence. MATERIAL AND METHODS: A single investigator reviewed records of patients treated by eight periodontics residents from July 2018 through June 2022. For each procedure, the investigator recorded each intraoperative and postoperative complication or indicated that no complication had occurred. These outcomes were analyzed against a panel of explanatory covariates. In addition, the severity of each postoperative complication was assessed using a standardized grading system. RESULTS: A total of 1135 procedures were included in the analysis. Intraoperative and postoperative complications were identified in 2.8% and 15.2% of procedures, respectively. The most common intraoperative complications were Schneiderian membrane perforation (1.3%) and gingival flap perforation/tear (1%), and the most common postoperative complications were dentin hypersensitivity (2.6%), excessive pain (2.5%), and infection (2.2%). Subepithelial connective tissue graft (odds ratio [OR]: 3.2, 95% confidence interval [CI]: 1.6, 6.1; p < .001), guided bone regeneration (OR: 3.0, 95% CI: 1.4, 6.5; p = .004), and guided bone regeneration with implant placement (OR: 3.1, 95% CI: 1.3, 7.6; p = .011) were associated with higher odds of postoperative complication, whereas lateral sinus elevation (OR: 102.5, 95% CI: 12.3, 852.9; p < .001), transalveolar sinus elevation (OR: 22.4, 95% CI: 2.2, 224.5; p = .008), open flap debridement (OR: 36.4, 95% CI: 3.0, 440.7; p = .005), and surgically facilitated orthodontic therapy (OR: 20.5, 95% CI: 1.2, 358.4; p = .039) were associated with higher odds of intraoperative complication occurrence. CONCLUSIONS: Consistent with previous reports, procedure type appears to be the predominant factor driving complication occurrence. As analyses of treatment complications increase, individualized risk-benefit assessments will become progressively meaningful for patients.


Subject(s)
Dental Implants , Sinus Floor Augmentation , Humans , Sinus Floor Augmentation/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Dental Implantation, Endosseous , Bone Transplantation/methods
17.
Clin Adv Periodontics ; 14(1): 38-51, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37555583

ABSTRACT

BACKGROUND: The physiologic bone remodeling accompanying tooth extraction is a phenomenon well described in the dental literature. Extraction sockets severely compromised by local infection, trauma, iatrogenesis, or other factors may exhibit enhanced reduction in alveolar dimensions during healing. The purpose of this report is to present an alveolar ridge preservation (ARP) protocol specifically intended for use at severely compromised sites. METHODS: Seven patients presented to the Department of Periodontics, Army Postgraduate Dental School, Fort Gordon, Georgia, requiring extraction of teeth with partial or near-complete loss of the facial/buccal cortex. At each site, a cross-linked bovine collagen membrane was used to prevent collapse of the facial/buccal soft tissue and maintain space, a freeze-dried bone allograft was applied in the socket, and a dense polytetrafluoroethylene membrane covered the occlusal aspect. RESULTS: All sites healed uneventfully and resulted in favorable alveolar ridge dimensions for implant placement. CONCLUSION: Few authors have proposed specific ARP methods for managing severely deficient extraction sockets. The predominant recommendation has been staged reconstruction of the site applying hard and soft tissue augmentation. Observations reported herein suggest that staged reconstruction is avoidable at some extraction sockets exhibiting severe alveolar compromise. Controlled clinical investigation of this protocol appears warranted. KEY POINTS: Few authors have proposed alveolar ridge preservation (ARP) methods specifically intended for use at severely compromised extraction sockets. The prevailing recommendation at such sites is a staged protocol involving tooth extraction with delayed hard and soft tissue augmentation. The presented bilaminar ARP technique may eliminate the need for staged reconstruction at some severely compromised extraction sockets.


Subject(s)
Alveolar Bone Loss , Alveolar Ridge Augmentation , Humans , Animals , Cattle , Tooth Socket/surgery , Tooth Socket/physiology , Alveolar Ridge Augmentation/methods , Alveolar Bone Loss/prevention & control , Alveolar Bone Loss/surgery , Alveolar Process/surgery , Collagen
18.
Article in English | MEDLINE | ID: mdl-38487961

ABSTRACT

BACKGROUND: Current evidence acknowledges guided bone regeneration (GBR) as a predictable therapeutic modality in the augmentation of a deficient alveolar ridge. Such deficiencies often reveal inadequate bone volume to support implant placement in a position amenable to prosthetic reconstruction. Additionally, an evolving body of literature demonstrates that membrane fixation may lead to improved clinical bone gain through positively influencing blood clot formation, stability, and the eventual osteogenic potential of the defect. Alternative benefits to membrane fixation, such as reduced graft displacement and reduction in wound micromotion, have also been cited as mechanisms for an increased regenerative response. METHODS AND RESULTS: The aim of this report was to present a case, including diagnosis, treatment, and follow-up for the reconstruction of a horizontal ridge deficiency. The patient's deficiency in ridge volume was found to be a developmental sequelae of lateral incisor agenesis, resulting in an underdeveloped midfacial region of the alveolar process subjacent to sites #7 and #10. The fixation protocol outlined in this report demonstrated adequate horizontal ridge augmentation to facilitate future prosthetic reconstruction with the use of implants. CONCLUSIONS: Numerous protocols have been established in an attempt to achieve effective barrier membrane stabilization for bone augmentation procedures. However, some techniques are poorly suited for the anatomically challenging region of the anterior maxilla. A case report describing the utilization of the anterior nasal spine for anchorage of a membrane-stabilizing suture may present a novel, safe, and effective technique for stabilizing the intended region of augmentation, as well as preventing graft migration beyond the membrane-maxilla interface. Key points Regarding guided bone regeneration (GBR) procedures, micromotion of the membrane or of the underlying particulate graft may negatively influence the volume of the augmented site. The ability to adequately stabilize the graft-membrane interface is recognized as a necessary prerequisite to predictably achieve optimal surgical outcomes. To the authors' knowledge, there is no clinical or scientific evidence regarding the use of the anterior nasal spine for membrane anchorage in maxillary GBR procedures, and thus a novel approach to membrane stabilization is introduced.

19.
J Dent Educ ; 88(4): 403-410, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38269493

ABSTRACT

PURPOSE/OBJECTIVES: The objectives of this study were to assess the influence of learner- and education-related factors on standardized in-service examination performance and determine whether in-service examination scores predict residency outcomes. METHODS: American Academy of Periodontology (AAP) In-service Examination (AIE) scores from 10 periodontics residency classes at a single center were recorded and compared against a panel of learner- and education-related variables using multiple linear regression models. Defined residency outcome measures were analyzed against AIE scores using binomial logistic regression. RESULTS: No evaluated learner- or education-related variable was a statistically significant predictor of AIE score in this study sample. Likewise, AIE score was not a statistically significant predictor of any assessed residency outcome. CONCLUSIONS: The AAP has performed a tremendous service to periodontics residents and programs by marshaling the leadership and expertise necessary to offer a professionally constructed assessment instrument. However, in the current study, no relationship could be identified between AIE score and any outcome, including first-attempt board certification. The AAP In-service Committee appears well situated to provide additional leadership focusing on exam implementation, which may enhance AIE value in competency decision making.


Subject(s)
Internship and Residency , United States , Education, Medical, Graduate , Periodontics , Educational Measurement , Clinical Competence
20.
Environ Sci Technol ; 47(6): 2542-7, 2013 Mar 19.
Article in English | MEDLINE | ID: mdl-23373764

ABSTRACT

The recent widespread adoption of compact fluorescent lamps (CFL) has increased their importance as a source of environmental Hg. Stable isotope analysis can identify the sources of environmental Hg, but the isotopic composition of Hg from CFL is not yet known. Results from analyses of CFL with a range of hours of use show that the Hg they contain is isotopically fractionated in a unique pattern during normal CFL operation. This fractionation is large by comparison to other known fractionating processes for Hg and has a distinctive, mass-independent signature, such that CFL Hg could be uniquely identified from other sources. The fractionation process described here may also explain anomalous fractionation of Hg isotopes in precipitation.


Subject(s)
Environmental Pollutants/analysis , Mercury/analysis , Chemical Fractionation , Chemical Precipitation , Fluorescence , Mercury Isotopes/analysis , Optics and Photonics
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