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1.
Environ Toxicol Chem ; 43(5): 1112-1125, 2024 May.
Article in English | MEDLINE | ID: mdl-38517160

ABSTRACT

Freshwater mussels provide invaluable ecological services but are threatened by habitat alteration, poor water quality, invasive species, climate change, and contaminants, including contaminants of emerging concern (CECs). Contaminants of emerging concerns are well documented in aquatic environments, including the Great Lakes Basin, but limited information is available on how environmentally relevant mixtures affect freshwater mussel biology throughout their varied life stages. Our main goal was to assess mussels' reproductive output in response to exposure to agricultural and urban CEC mixtures during glochidial development through juvenile transformation and excystment focusing on how exposure duration and treatment affect: (1) the number of glochidia prematurely released by brooding females, (2) glochidial transformation through host-fish excystment, and (3) the number of fully metamorphosed juveniles able to continue the lifecycle. Mussels and host fish were exposed to either a control water (CW), control ethanol (CE), agriculture CEC mixture (AM), or urban CEC mixture (UM) for 40 and 100 days. We found no effect from treatment or exposure duration on the number of glochidia prematurely released. Fewer partially and fully metamorphosed AM juveniles were observed during the 100-day exposure, compared with the 40-day. During the 40-day exposure, CW produced more fully metamorphosed individuals compared with CE and UM, but during the 100-day exposure AM produced more fully metamorphosed individuals compared with the CW. There was reduction in fully metamorphosed juveniles compared with partially metamorphosed for CE and UM during the 40-day exposure, as well as in the CW during the 100-day exposure. These results will be important for understanding how mussel populations are affected by CEC exposure. The experiments also yielded many insights for laboratory toxicology exposure studies. Environ Toxicol Chem 2024;43:1112-1125. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.


Subject(s)
Water Pollutants, Chemical , Animals , Water Pollutants, Chemical/toxicity , Fresh Water , Agriculture , Bivalvia/drug effects , Bivalvia/growth & development , Reproduction/drug effects , Ethanol/toxicity , Cities , Female
2.
Harmful Algae ; 131: 102548, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38212081

ABSTRACT

Cyanotoxins produced by harmful cyanobacteria blooms can damage freshwater ecosystems and threaten human health. Floating macrophytes may be used as a means of biocontrol by limiting light and resources available to cyanobacteria. However, genetic variation in macrophyte sensitivity to cyanotoxins could influence their suitability as biocontrol agents. We investigated the influence of such intraspecific variation on the response of two rapidly growing duckweed species, Lemna minor and Spirodela polyrhiza, often used in nutrient and metal bioremediation. We assessed two biomarkers related to productivity (biomass and chlorophyll A production) and two related to fitness measures (population size and growth rate). Fifteen genetic lineages of each species were grown in media containing common cyanotoxin microcystin-LR at ecologically relevant concentrations or control media for a period of twelve days. Genotype identity had a strong impact on all biomarker responses. Microcystin concentration slightly increased the final population sizes of both macrophyte species with a marginal effect on growth rate of L. minor and the chlorophyll A production of S. polyrhiza, but overall these species were very tolerant of microcystin. The strong tolerance supports the potential use of these plants as bioremediators of cyanobacterial blooms. However, differential impact of microcystin exposure discovered in single lineage models among genotypes indicates a potential for cyanotoxins to act as selective forces, necessitating attention to genotype selection for bioremediation.


Subject(s)
Araceae , Cyanobacteria , Marine Toxins , Humans , Microcystins , Chlorophyll A , Ecosystem , Araceae/genetics , Cyanobacteria Toxins , Cyanobacteria/genetics
3.
iScience ; 26(11): 108224, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-38107878

ABSTRACT

Menstruating individuals without access to adequate hygiene products often improvise with alternatives that pose health risks and limit their participation in society. We describe here a menstrual hygiene product based on low-cost materials, which are integrated onto fabrics to imbue unidirectional permeability. A body-facing "Janus" fabric top layer comprising ZnO tetrapods spray-coated onto polyester mosquito netting imparts hierarchical texturation, augmenting the micron-scale texturation derived from the weave of the underlying fabric. The asymmetric coating establishes a gradient in wettability, which underpins flash spreading and unidirectional permeability. The hygiene product accommodates a variety of absorptive media, which are sandwiched between the Janus layer and a second outward-facing coated densely woven fabric. An assembled prototype demonstrates outstanding ability to wick saline solutions and a menstrual fluid simulant while outperforming a variety of commercially alternatives. The results demonstrate a versatile menstrual health product that provides a combination of dryness, discretion, washability, and safety.

4.
Antimicrob Agents Chemother ; 67(6): e0017223, 2023 06 15.
Article in English | MEDLINE | ID: mdl-37133362

ABSTRACT

A novel Bayesian method was developed to interpret serum vancomycin concentrations (SVCs) following the administration of one or more vancomycin doses with potential varying doses and intervals based on superposition principles. The method was evaluated using retrospective data from 442 subjects from three hospitals. The patients were required to receive vancomycin for more than 3 days, have stable renal function (fluctuation in serum creatinine of ≤0.3 mg/dL), and have at least 2 trough concentrations reported. Pharmacokinetic parameters were predicted using the first SVC, and the fitted parameters were then used to predict subsequent SVCs. Using only covariate-adjusted population prior estimates, the first two SVC prediction errors were 47.3 to 54.7% for the scaled mean absolute error (sMAE) and 62.1 to 67.8% for the scaled root mean squared error (sRMSE). "Scaled" refers to the division of the MAE or RMSE by the mean value. The Bayesian method had minimal errors for the first SVC (by design), and for the second SVC, the sMAE was 8.95%, and the sRMSE was 36.5%. The predictive performance of the Bayesian method did degrade with subsequent SVCs, which we attributed to time-dependent pharmacokinetics. The 24-h area under the concentration-time curve (AUC) was determined from simulated concentrations before and after the first SVC was reported. Prior to the first SVC, 170 (38.4%) patients had a 24-h AUC of <400 mg · h/L, 186 (42.1%) had a 24-h AUC within the target range, and 86 (19.5%) had a 24-h AUC of >600 mg · h/L. After the first SVC was reported, 322 (72.9%) had a 24-h AUC within the target range, 68 (15.4%) had low values, and 52 (11.8%) had high values based on the model simulation. Target attainments were 38% before the first SVC and 73% after the first SVC. The hospitals had no policies or procedures in place for targeting 24-h AUCs, although the trough target was typically 13 to 17 mg/L. Our data provide evidence of time-dependent pharmacokinetics, which will require regular therapeutic drug monitoring regardless of the method used to interpret SVCs.


Subject(s)
Drug Monitoring , Vancomycin , Humans , Bayes Theorem , Retrospective Studies , Area Under Curve , Drug Monitoring/methods , Anti-Bacterial Agents
6.
Ecotoxicology ; 32(4): 451-468, 2023 May.
Article in English | MEDLINE | ID: mdl-37079163

ABSTRACT

Highly imperiled unionids have a complex life cycle including the metamorphosis of an obligate parasite life stage, larval glochidia, to the juvenile stage. Despite the known vulnerabilities of both glochidia and juveniles to pollutants, little is known on how metamorphosis success may be affected by chemical stress. Disruption of the transformation process in which glochidia encyst on the gills of a host fish, could lead to lowered recruitment and population declines. Transformation rates of Lampsilis cardium on host fish Micropterus salmoides were empirically derived from experimental exposures to low, medium, or high concentrations of an agricultural or urban mixture of contaminants of emerging concern (CECs) over two exposure durations. Transformation was characterized by: (1) a zero-inflated Poisson general linear mixed effects model to compare difference in transformation between exposure durations and (2) time response curves to describe the transformation curve using long-term exposure data. Lampsilis cardium transformation was similar between exposure durations. When compared to controls, CEC stress significantly reduced juvenile production (p « 0.05) except for the agricultural medium treatment and tended to increased encapsulation duration which while statistically insignificant (p = 0.16) may have ecological relevancy. Combining the empirically derived reduction of transformation rates with parameters values from the literature, a Lefkovich stage-based population model predicted strong declines in population size of L. cardium for all treatments if these results hold in nature. Management focus on urban CECs may lead to best conservation efforts though agricultural CECs may also have a concentration dependent impact on transformation and therefore overall recruitment and conservation success.


Subject(s)
Bass , Bivalvia , Unionidae , Water Pollutants, Chemical , Animals , Water Pollutants, Chemical/toxicity , Larva , Metamorphosis, Biological
7.
J Clin Oncol ; 41(2): 233-242, 2023 01 10.
Article in English | MEDLINE | ID: mdl-35981270

ABSTRACT

PURPOSE: Organ-sparing therapy for early-stage I/IIA rectal cancer is intended to avoid functional disturbances or a permanent ostomy associated with total mesorectal excision (TME). The objective of this phase II trial was to determine the outcomes and organ-sparing rate of patients with early-stage rectal cancer treated with neoadjuvant chemotherapy followed by transanal excision surgery (TES). METHODS: This phase II trial included patients with clinical T1-T3abN0 low- or mid-rectal adenocarcinoma eligible for endoscopic resection who were treated with 3 months of chemotherapy (modified folinic acid-fluorouracil-oxaliplatin 6 or capecitabine-oxaliplatin). Those with evidence of response proceeded to transanal endoscopic surgery 2-6 weeks later. The primary end point was protocol-specified organ preservation rate, defined as the proportion of patients with tumor downstaging to ypT0/T1N0/X and who avoided radical surgery. RESULTS: Of 58 patients enrolled, all commenced chemotherapy and 56 proceeded to surgery. A total of 33/58 patients had tumor downstaging to ypT0/1N0/X on the surgery specimen, resulting in an intention-to-treat protocol-specified organ preservation rate of 57% (90% CI, 45 to 68). Of 23 remaining patients recommended for TME surgery on the basis of protocol requirements, 13 declined and elected to proceed directly to observation resulting in 79% (90% CI, 69 to 88) achieving organ preservation. The remaining 10/23 patients proceeded to recommended TME of whom seven had no histopathologic residual disease. The 1-year and 2-year locoregional relapse-free survival was, respectively, 98% (95% CI, 86 to 100) and 90% (95% CI, 58 to 98), and there were no distant recurrences or deaths. Minimal change in quality of life and rectal function scores was observed. CONCLUSION: Three months of induction chemotherapy may successfully downstage a significant proportion of patients with early-stage rectal cancer, allowing well-tolerated organ-preserving surgery.


Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Humans , Oxaliplatin/therapeutic use , Quality of Life , Neoplasm Staging , Neoplasm Recurrence, Local/drug therapy , Rectal Neoplasms/drug therapy , Rectal Neoplasms/surgery , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Treatment Outcome
8.
ACS Omega ; 7(2): 1547-1574, 2022 Jan 18.
Article in English | MEDLINE | ID: mdl-35071852

ABSTRACT

An increasing global population and a sharply upward trajectory of per capita energy consumption continue to drive the demand for fossil fuels, which remain integral to energy grids and the global transportation infrastructure. The oil and gas industry is increasingly reliant on unconventional deposits such as heavy crude oil and bitumen for reasons of accessibility, scale, and geopolitics. Unconventional deposits such as the Canadian Oil Sands in Northern Alberta contain more than one-third of the world's viscous oil reserves and are vital linchpins to meet the energy needs of rapidly industrializing populations. Heavy oil is typically recovered from subsurface deposits using thermal recovery approaches such as steam-assisted gravity drainage (SAGD). In this perspective article, we discuss several aspects of materials science challenges in the utilization of heavy crude oil with an emphasis on the needs of the Canadian Oil Sands. In particular, we discuss surface modification and materials' design approaches essential to operations under extreme environments of high temperatures and pressures and the presence of corrosive species. The demanding conditions for materials and surfaces are directly traceable to the high viscosity, low surface tension, and substantial sulfur content of heavy crude oil, which necessitates extensive energy-intensive thermal processes, warrants dilution/emulsification to ease the flow of rheologically challenging fluids, and engenders the need to protect corrodible components. Geopolitical reasons have further led to a considerable geographic separation between extraction sites and advanced refineries capable of processing heavy oils to a diverse slate of products, thus necessitating a massive midstream infrastructure for transportation of these rheologically challenging fluids. Innovations in fluid handling, bitumen processing, and midstream transportation are critical to the economic viability of heavy oil. Here, we discuss foundational principles, recent technological advancements, and unmet needs emphasizing candidate solutions for thermal insulation, membrane-assisted separations, corrosion protection, and midstream bitumen transportation. This perspective seeks to highlight illustrative materials' technology developments spanning the range from nanocomposite coatings and cement sheaths for thermal insulation to the utilization of orthogonal wettability to engender separation of water-oil emulsions stabilized by endogenous surfactants extracted during SAGD, size-exclusion membranes for fractionation of bitumen, omniphobic coatings for drag reduction in pipelines and to ease oil handling in containers, solid prills obtained from partial bitumen solidification to enable solid-state transport with reduced risk of damage from spills, and nanocomposite coatings incorporating multiple modes of corrosion inhibition. Future outlooks for onsite partial upgradation are also described, which could potentially bypass the use of refineries for some fractions, enable access to a broader cross-section of refineries, and enable a new distributed chemical manufacturing paradigm.

9.
Mater Horiz ; 9(1): 452-461, 2022 Jan 04.
Article in English | MEDLINE | ID: mdl-34846413

ABSTRACT

Low-cost and scalable superhydrophobic coating methods provide viable approaches for energy-efficient separation of immiscible liquid/liquid mixtures. A scalable photopolymerization method is developed to functionalize porous substrates with a hybrid coating of tetrapodal ZnO (T-ZnO) and polymethacrylate, which exhibits simultaneous superhydrophobicity and superoleophilicity. Here, T-ZnO serves dual purposes by (i) initiating radical photopolymerization during the fabrication process through a hole-mediated pathway and (ii) providing a hierarchical surface roughness to amplify wettability characteristics and suspend liquid droplets in the metastable Cassie-Baxter regime. Photopolymerization provides a means to finely control the conversion and spatial distribution of the formed polymer, whilst allowing for facile large-area fabrication and potential coating on heat-sensitive substrates. Coated stainless-steel meshes and filter papers with desired superhydrophobic/superoleophilic properties exhibit excellent performance in separating stratified oil/water, oil/ionic-liquid, and water/ionic-liquid mixtures as well as water-in-oil emulsions. The hybrid coating demonstrates desired mechanical robustness and chemical resistance for their long-term application in large-scale energy-efficient separation of immiscible liquid/liquid mixtures.

10.
Sci Total Environ ; 801: 149732, 2021 Dec 20.
Article in English | MEDLINE | ID: mdl-34438156

ABSTRACT

Herbicides can drift from intended plants onto non-target species. It remains unclear how drift impacts plant functional traits that are important for fitness. To address this gap, we conducted an experiment where fast cycling Brassica rapa plants were exposed to one of three drift concentrations (0.5%, 1%, 10%) of synthetic-auxin dicamba. We evaluated damage to and capacity of floral and vegetative traits to recover as well as lifetime fitness by comparing treated plants to controls. Response to dicamba exposure was concentration-dependent across all traits but varied with trait type. At 0.5% dicamba, three out of five floral traits were affected, while at 1% dicamba, four floral traits and one out of two vegetative traits were negatively impacted. At 10% dicamba all floral and vegetative traits were stunted. Overall, floral traits were more responsive to all dicamba drift concentrations than vegetative traits and displayed a wide range of variation ranging from no response (e.g., pistil length) to up to 84% reduction (ovule number). However, despite floral traits were more affected across the dicamba drift concentrations they were also more likely to recover than the vegetative traits. There was also variation among lifetime traits; the onset of flowering was delayed, and reproductive fitness was negatively affected in a concentration-dependent manner, but the final biomass and total flower production were not affected. Altogether, we show substantial variation across plant traits in their response to dicamba and conclude that accounting for this variation is essential to understand the full impact of herbicide drift on plants and the ecological interactions these traits mediate.


Subject(s)
Brassica rapa , Herbicides , Brassica rapa/genetics , Dicamba/toxicity , Flowers , Herbicides/toxicity , Indoleacetic Acids
11.
J Cutan Med Surg ; 23(6): 586-594, 2019.
Article in English | MEDLINE | ID: mdl-31462069

ABSTRACT

BACKGROUND: Melanoma incidence increases with socioeconomic status but the effect of rurality and access to primary care or dermatology on patient outcomes is unclear. OBJECTIVES: The objectives of this study were to determine whether access to care, rurality, or socioeconomic status are associated with melanoma stage at presentation and prognosis. METHODS: Linked administrative databases from Ontario, Canada, were retrospectively analyzed to identify a population-based cohort of patients diagnosed with melanoma between 2004 and 2012. Rurality was assessed using the rural index of Ontario (RIO) score, and the number of visits to dermatology and primary care was used to evaluate access to care. RESULTS: We identified 18 776 melanoma patients, of whom 9591 had completed pathological staging. Patients with higher RIO scores, living further from a cancer center or in a rural community, were less likely to see a dermatologist in the year prior to diagnosis (P < .001 for all). Patients seen by a dermatologist within 365 days prior to diagnosis were less likely to present with stage III or IV disease (odds ratio 0.63, P < .001) and had improved overall survival (hazard ratio [HR] for death 0.77, P < .001). There was a nonlinear association between number of family physician visits and melanoma prognosis, with patients who had 3 to 5 visits per year having the best overall survival (HR 0.88, P = .003). CONCLUSION: Our findings strengthen the known association between access to dermatology and melanoma outcomes by linking individual patients' prediagnosis access to care to pathological stage at diagnosis and overall survival.


Subject(s)
Health Services Accessibility/statistics & numerical data , Melanoma , Skin Neoplasms , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Melanoma/epidemiology , Melanoma/mortality , Melanoma/pathology , Melanoma/therapy , Middle Aged , Ontario/epidemiology , Prognosis , Retrospective Studies , Skin Neoplasms/epidemiology , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Young Adult
12.
ACS Appl Mater Interfaces ; 9(44): 38887-38900, 2017 Nov 08.
Article in English | MEDLINE | ID: mdl-29039916

ABSTRACT

Buildings consume an inordinate amount of energy, accounting for 30-40% of worldwide energy consumption. A major portion of solar radiation is transmitted directly to building interiors through windows, skylights, and glazed doors where the resulting solar heat gain necessitates increased use of air conditioning. Current technologies aimed at addressing this problem suffer from major drawbacks, including a reduction in the transmission of visible light, thereby resulting in increased use of artificial lighting. Since currently used coatings are temperature-invariant in terms of their solar heat gain modulation, they are unable to offset cold-weather heating costs that would otherwise have resulted from solar heat gain. There is considerable interest in the development of plastic fenestration elements that can dynamically modulate solar heat gain based on the external climate and are retrofittable onto existing structures. The metal-insulator transition of VO2 is accompanied by a pronounced modulation of near-infrared transmittance as a function of temperature and can potentially be harnessed for this purpose. Here, we demonstrate that a nanocomposite thin film embedded with well dispersed sub-100-nm diameter VO2 nanocrystals exhibits a combination of high visible light transmittance, effective near-infrared suppression, and onset of NIR modulation at wavelengths <800 nm. In our approach, hydrothermally grown VO2 nanocrystals with <100 nm diameters are dispersed within a methacrylic acid/ethyl acrylate copolymer after either (i) grafting of silanes to constitute an amorphous SiO2 shell or (ii) surface functionalization with perfluorinated silanes and the use of a perfluorooctanesulfonate surfactant. Homogeneous and high optical quality thin films are cast from aqueous dispersions of the pH-sensitive nanocomposites onto glass. An entirely aqueous-phase process for preparation of nanocrystals and their effective dispersion within polymeric nanocomposites allows for realization of scalable and viable plastic fenestration elements.

13.
J Pediatr Nurs ; 34: 65-71, 2017.
Article in English | MEDLINE | ID: mdl-28094094

ABSTRACT

OBJECTIVES: To describe the development of a new skin risk assessment scale called Skin Injury Risk Assessment and Prevention (SIRA+P) and to establish initial reliability and validity of the scale among patients ranging in age from birth, including pre-term, to adulthood, regardless of age or acuity of illness. STUDY DESIGN: The single-site study was a retrospective chart review to evaluate the measurement properties of SIRA+P. Charts of 385 patients of all ages and in all units (including the neonatal and pediatric intensive care units) of a free-standing children's hospital were included. Concurrent validity was assessed with scales having previously established reliability and validity. For subjects <30days of age, the comparison scale was the Neonatal Skin Risk Assessment Scale (NSRAS); for subjects 31days through 17years, the Braden Q Scale (Braden Q) was used; and for subjects 18years and older, the Braden Scale (Braden) was used. Interrater reliability was examined using Intraclass Correlation Coefficients (ICC). Concurrent validity procedures compared SIRA+P with NSRAS, Braden Q, and Braden using Pearson Correlation Coefficients. RESULTS: Interrater reliability for SIRA+P was very high (0.878). SIRA+P strongly correlated with the NSRAS (0.725), the Braden Q (-0.634), and the Braden (-0.778). CONCLUSION: SIRA+P is designed to be used within the EHR and includes nursing decision support to guide pressure injury prevention interventions for specific skin integrity risks. SIRA+P has good interrater reliability, is valid across all age groups and accounts for device-related pressure.


Subject(s)
Pressure Ulcer/diagnosis , Pressure Ulcer/epidemiology , Risk Assessment/methods , Skin Care/methods , Skin/injuries , Adolescent , Age Distribution , Child , Child, Hospitalized , Child, Preschool , Clinical Decision-Making , Cohort Studies , Female , Hospitals, Pediatric , Humans , Incidence , Infant , Infant, Newborn , Male , Nursing Assessment , Observer Variation , Pediatric Nursing/organization & administration , Physical Examination/methods , Pressure Ulcer/prevention & control , Prognosis , Reproducibility of Results , Retrospective Studies , Severity of Illness Index , Sex Distribution
14.
Subcell Biochem ; 80: 255-69, 2014.
Article in English | MEDLINE | ID: mdl-24798016

ABSTRACT

Chlamydiae are obligate intracellular bacterial parasites that infect a wide range of metazoan hosts. Some Chlamydia species are important causes of chronic inflammatory diseases of the ocular, genital and respiratory tracts in humans. Genes located in a variable region of chlamydial genomes termed the plasticity zone are known to be key determinants of pathogenic diversity. The plasticity zone protein CT153, present only in select species, contains a membrane attack complex/perforin (MACPF) domain, which may mediate chlamydial interactions with the host cell. CT153 is present throughout the C. trachomatis developmental cycle and is processed into polypeptides that interact with membranes differently than does the parent protein. Chlamydiae interact extensively with membranes from the time of invasion until they eventually exit host cells, so numerous roles for a MACPF protein in pathogenesis of these pathogens are conceivable. Here, we present an overview of what is known about CT153 and highlight potential roles of a MACPF family protein in a group of pathogens whose intracellular development is marked by a series of interactions with host cell membranes and organelles. Finally, we identify new strategies for identifying CT153 functions made feasible by the recent development of a basic toolset for genetic manipulation of chlamydiae.


Subject(s)
Bacterial Proteins/physiology , Chlamydia trachomatis , Complement Membrane Attack Complex/physiology , Perforin/physiology , Animals , Bacterial Proteins/chemistry , Chlamydia Infections/microbiology , Chlamydia trachomatis/genetics , Chlamydia trachomatis/growth & development , Chlamydia trachomatis/pathogenicity , Complement Membrane Attack Complex/chemistry , Host-Pathogen Interactions , Humans , Perforin/chemistry
15.
Infect Immun ; 82(7): 2756-62, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24733093

ABSTRACT

Chlamydia trachomatis is an obligate intracellular mucosotropic pathogen of significant medical importance. It is the etiological agent of blinding trachoma and bacterial sexually transmitted diseases, infections that afflict hundreds of millions of people globally. The C. trachomatis polymorphic membrane protein D (PmpD) is a highly conserved autotransporter and the target of broadly cross-reactive neutralizing antibodies; however, its role in host-pathogen interactions is unknown. Here we employed a targeted reverse genetics approach to generate a pmpD null mutant that was used to define the role of PmpD in the pathogenesis of chlamydial infection. We show that pmpD is not an essential chlamydial gene and the pmpD null mutant has no detectable deficiency in cultured murine cells or in a murine mucosal infection model. Notably, however, the pmpD null mutant was significantly attenuated for macaque eyes and cultured human cells. A reduction in pmpD null infection of human endocervical cells was associated with a deficiency in chlamydial attachment to cells. Collectively, our results show that PmpD is a chlamydial virulence factor that functions in early host-cell interactions. This study is the first of its kind using reverse genetics to evaluate the contribution of a C. trachomatis gene to disease pathogenesis.


Subject(s)
Bacterial Proteins/metabolism , Chlamydia Infections/microbiology , Chlamydia trachomatis/metabolism , Membrane Proteins/metabolism , Virulence Factors/metabolism , Animals , Bacterial Proteins/genetics , Cell Line , Female , Gene Expression Regulation, Bacterial , Host-Pathogen Interactions , Humans , Macaca fascicularis , Male , Membrane Proteins/genetics , Mice , Mice, Inbred C3H , Mutation
16.
J Clin Microbiol ; 51(11): 3579-84, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23966484

ABSTRACT

Assays that expedite the reporting of organism identification and antibiotic susceptibility status in positive blood cultures can fast track interventions that improve clinical outcomes. We evaluated the Verigene Gram-positive blood culture nucleic acid test (BC-GP) in two pediatric hospitals. Positive BacT/Alert Pediatric FAN blood cultures with Gram-positive organisms were tested using the BC-GP in tandem with routine laboratory procedures. To test organisms underrepresented in the clinical blood culture evaluation, blood culture bottles were spiked with diluted organism suspensions at concentrations of 10 to 100 CFU per milliliter. A total of 249 Gram-positive bacterial isolates were recovered from 242 blood cultures. The BC-GP detected Staphylococcus aureus, methicillin-susceptible S. aureus, and methicillin-resistant S. aureus with sensitivities of 100%, 99%, and 100% and specificities of 100%, 100%, and 99.5%, respectively. The BC-GP detected Staphylococcus epidermidis, methicillin-susceptible S. epidermidis, and methicillin-resistant S. epidermidis with sensitivities of 95%, 80%, and 96%, respectively, and 100% specificity. The BC-GP correctly identified 14/15 cases of Enterococcus faecalis and Enterococcus faecium bacteremia and 9 cases of Streptococcus pneumoniae. It misidentified 5/15 clinical blood cultures with Streptococcus mitis/Streptococcus oralis and 1/3 blood cultures spiked with Streptococcus anginosus group as S. pneumoniae. The BC-GP detected a case of Streptococcus pyogenes bacteremia but failed to detect 2/3 clinical blood cultures with Streptococcus agalactiae. BC-GP's rapid accurate detection of Staphylococcus spp., E. faecium, and E. faecalis and its ability to ascertain mecA, vanA, and vanB status may expedite clinical decisions pertaining to optimal antibiotic use. False-positive S. pneumoniae results may warrant reporting of only "Streptococcus spp." when this organism is reported by the BC-GP.


Subject(s)
Bacteriological Techniques/methods , Enterococcus/isolation & purification , Gram-Positive Bacterial Infections/diagnosis , Molecular Diagnostic Techniques/methods , Staphylococcus/isolation & purification , Streptococcus/isolation & purification , Enterococcus/classification , Enterococcus/genetics , Hospitals, Pediatric , Humans , Sensitivity and Specificity , Staphylococcus/classification , Staphylococcus/genetics , Streptococcus/classification , Streptococcus/genetics
17.
J Foot Ankle Surg ; 51(3): 317-22, 2012.
Article in English | MEDLINE | ID: mdl-22285499

ABSTRACT

Mobility, especially in elderly patients, is often a proxy for overall health. It is thus of interest to understand the rates of lower extremity amputation and the risk factors for these procedures in the trauma population. We compared the rates of lower extremity amputation in low- versus high-level trauma by analyzing the National Trauma Data Bank. We also attempted to identify the risk factors in the low-level trauma population with foot and ankle trauma that predispose to lower extremity amputation. The factors associated with lower extremity amputation in foot and ankle trauma differed slightly from those in other multi-trauma patients. The factors associated with lower extremity amputation in the low-level foot and ankle trauma population that were statistically and clinically significant in this study included male gender, confounding injury, other trauma type versus blunt trauma, penetrating versus blunt trauma, occurrence of fracture, and occurrence of crush injury or wound. Understanding these risk factors will assist in educating patients and their family about their prognosis. Also, understanding these risk factors will assist surgeons with patient selection when considering salvage procedures.


Subject(s)
Amputation, Surgical/statistics & numerical data , Ankle Injuries/surgery , Ankle/surgery , Foot Injuries/surgery , Foot/surgery , Risk Assessment/methods , Adult , Ankle Injuries/epidemiology , Female , Follow-Up Studies , Foot Injuries/epidemiology , Humans , Incidence , Injury Severity Score , Male , Retrospective Studies , Risk Factors , Texas/epidemiology
18.
J Foot Ankle Surg ; 51(1): 30-3, 2012.
Article in English | MEDLINE | ID: mdl-22036147

ABSTRACT

Timely incorporation of bone grafts is essential to the structural rigidity in most foot and ankle surgeries. Although bovine-based xenografts possess some of the key features necessary for foot and ankle surgery, the studies evaluating the efficacy of these grafts are limited. The aim of the present study was to determine the incorporation rate of bovine-based bone grafts in foot surgery. A total of 22 patients who had undergone reconstructive foot surgery using 31 bovine-based xenografts were identified, and the rate of radiographic incorporation of the grafts was evaluated. A survival analysis was used to show the trend of the incorporation of the xenografts over time. Of the 21 grafts observed for at least 12 weeks, none showed radiographic graft incorporation by 12 weeks. The analogous numbers for 24, 36, and 48 weeks were 3 (20%) of 15, 4 (31%) of 13, and 3 (27%) of 11 grafts. A total of 19 (61.29%) of the 31 grafts studied were never observed to have incorporated radiographically, for the entire observation period. A Kaplan-Meier estimate revealed the median interval to graft incorporation was 56 weeks. Compared with previous studies, which investigated the incorporation of other types of grafts, such as autograft and allografts, we believe that xenografts incorporate more slowly. For this reason, such grafts might not be ideal for use in reconstructive foot surgery.


Subject(s)
Bone Transplantation , Foot Bones/surgery , Adolescent , Adult , Animals , Cattle , Child , Cohort Studies , Female , Graft Survival , Humans , Male , Middle Aged , Osseointegration , Osteotomy , Retrospective Studies , Transplantation, Heterologous , Young Adult
19.
J Exp Med ; 208(11): 2217-23, 2011 Oct 24.
Article in English | MEDLINE | ID: mdl-21987657

ABSTRACT

Blinding trachoma is an ancient neglected tropical disease caused by Chlamydia trachomatis for which a vaccine is needed. We describe a live-attenuated vaccine that is safe and efficacious in preventing trachoma in nonhuman primates, a model with excellent predictive value for humans. Cynomolgus macaques infected ocularly with a trachoma strain deficient for the 7.5-kb conserved plasmid presented with short-lived infections that resolved spontaneously without ocular pathology. Multiple infections with the attenuated plasmid-deficient strain produced no inflammatory ocular pathology but induced an anti-chlamydial immune response. Macaques vaccinated with the attenuated strain were either solidly or partially protected after challenge with virulent plasmid-bearing organisms. Partially protected macaques shed markedly less infectious organisms than controls. Immune correlates of protective immunity were not identified, but we did detect a correlation between MHC class II alleles and solid versus partial protection. Epidemiological models of trachoma control indicate that a vaccine with this degree of efficacy would significantly reduce the prevalence of infection and rates of reinfection, known risk factors which drive blinding disease.


Subject(s)
Chlamydia trachomatis/immunology , Chlamydia trachomatis/pathogenicity , Trachoma/microbiology , Trachoma/prevention & control , Vaccines, Attenuated/therapeutic use , Animals , Chlamydia trachomatis/genetics , Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class II/immunology , Humans , Macaca fascicularis/genetics , Macaca fascicularis/immunology , Major Histocompatibility Complex , Trachoma/epidemiology
20.
J Foot Ankle Surg ; 50(4): 510-3, 2011.
Article in English | MEDLINE | ID: mdl-21536460

ABSTRACT

Medial column fusion is becoming increasingly popular for flatfoot reconstruction. The authors describe a new technique for medial column arthrodesis via tension band mesh plating. Plating on the tension side would provide dynamic compression of the arthrodesis sites via weightbearing. This technique may be useful to allow patients to bear weight early in the postoperative course after flatfoot reconstruction.


Subject(s)
Flatfoot/surgery , Orthopedic Procedures/methods , Plastic Surgery Procedures/methods , Surgical Mesh , Humans , Prosthesis Design , Treatment Outcome
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