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1.
Ann Surg ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385252

RESUMO

OBJECTIVE: To develop a severity-adjusted, hospital-level benchmarking comparative performance report for postoperative organ space infection and antibiotic utilization in children with complicated appendicitis. BACKGROUND: No benchmarking data exist to aid hospitals in identifying and prioritizing opportunities for infection prevention or antimicrobial stewardship in children with complicated appendicitis. METHODS: This was a multicenter cohort study using NSQIP-Pediatric data from 16 hospitals participating in a regional research consortium, augmented with antibiotic utilization data obtained through supplemental chart review. Children with complicated appendicitis who underwent appendectomy from 07/01/2015 to 06/30/2020 were included. Thirty-day postoperative OSI rates and cumulative antibiotic utilization were compared between hospitals using observed-to-expected (O/E) ratios after adjusting for disease severity using mixed effects models. Hospitals were considered outliers if the 95% confidence interval for O/E ratios did not include 1.0. RESULTS: 1790 patients were included. Overall, the OSI rate was 15.6% (hospital range: 2.6-39.4%) and median cumulative antibiotic utilization was 9.0 days (range: 3.0-13.0). Across hospitals, adjusted O/E ratios ranged 5.7-fold for OSI (0.49-2.80, P=0.03) and 2.4-fold for antibiotic utilization (0.59-1.45, P<0.01). Three (19%) hospitals were outliers for OSI (1 high and 2 low performers), and eight (50%) were outliers for antibiotic utilization (5 high and 3 low utilizers). Ten (63%) hospitals were identified as outliers in one or both measures. CONCLUSIONS: A comparative performance benchmarking report may help hospitals identify and prioritize quality improvement opportunities for infection prevention and antimicrobial stewardship, as well as identify exemplar performers for dissemination of best practices.

2.
JAMA Surg ; 159(5): 511-517, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38324276

RESUMO

Importance: Gangrenous, suppurative, and exudative (GSE) findings have been associated with increased surgical site infection (SSI) risk and resource use in children with nonperforated appendicitis. Establishing the role for postoperative antibiotics may have important implications for infection prevention and antimicrobial stewardship. Objective: To compare SSI rates in children with nonperforated appendicitis with GSE findings who did and did not receive postoperative antibiotics. Design, Setting, and Participants: This was a retrospective cohort study using American College of Surgeons' National Surgical Quality Improvement Program (NSQIP)-Pediatric Appendectomy Targeted data from 16 hospitals participating in a regional research consortium. NSQIP data were augmented with operative report and antibiotic use data obtained through supplemental medical record review. Children with nonperforated appendicitis with GSE findings who underwent appendectomy between July 1, 2015, and June 30, 2020, were identified using previously validated intraoperative criteria. Data were analyzed from October 2022 to July 2023. Exposure: Continuation of antibiotics after appendectomy. Main Outcomes and Measures: Rate of 30-day postoperative SSI including both incisional and organ space infections. Complementary hospital and patient-level analyses were conducted to explore the association between postoperative antibiotic use and severity-adjusted outcomes. The hospital-level analysis explored the correlation between postoperative antibiotic use and observed to expected (O/E) SSI rate ratios after adjusting for differences in disease severity (presence of gangrene and postoperative length of stay) among hospital populations. In the patient-level analysis, propensity score matching was used to balance groups on disease severity, and outcomes were compared using mixed-effects logistic regression to adjust for hospital-level clustering. Results: A total of 958 children (mean [SD] age, 10.7 [3.7] years; 567 male [59.2%]) were included in the hospital-level analysis, of which 573 (59.8%) received postoperative antibiotics. No correlation was found between hospital-level SSI O/E ratios and postoperative antibiotic use when analyzed by either overall rate of use (hospital median, 53.6%; range, 31.6%-100%; Spearman ρ = -0.10; P = .71) or by postoperative antibiotic duration (hospital median, 1 day; range, 0-7 days; Spearman ρ = -0.07; P = .79). In the propensity-matched patient-level analysis including 404 patients, children who received postoperative antibiotics had similar rates of SSI compared with children who did not receive postoperative antibiotics (3 of 202 [1.5%] vs 4 of 202 [2.0%]; odds ratio, 0.75; 95% CI, 0.16-3.39; P = .70). Conclusions and Relevance: Use of postoperative antibiotics did not improve outcomes in children with nonperforated appendicitis with gangrenous, suppurative, or exudative findings.


Assuntos
Antibacterianos , Apendicectomia , Apendicite , Gangrena , Infecção da Ferida Cirúrgica , Adolescente , Criança , Feminino , Humanos , Masculino , Antibacterianos/uso terapêutico , Apendicite/cirurgia , Cuidados Pós-Operatórios , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia
3.
Ann Surg ; 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37970676

RESUMO

OBJECTIVE: To compare rates of postoperative drainage and culture profiles in children with complicated appendicitis treated with the two most common antibiotic regimens with and without antipseudomonal activity (piperacillin-tazobactam [PT] and ceftriaxone with metronidazole [CM]). SUMMARY OF BACKGROUND DATA: Variation in use of antipseudomonal antibiotics has been driven by a paucity of multicenter data reporting clinically relevant, culture-based outcomes. METHODS: Retrospective cohort study of patients with complicated appendicitis (7/2015-6/2020) using NSQIP-Pediatric data from 15 hospitals participating in a regional research consortium. Operative report details, antibiotic utilization, and culture data were obtained through supplemental chart review. Rates of 30-day postoperative drainage and organism-specific culture positivity were compared between groups using mixed effects regression to adjust for clustering after propensity matching on measures of disease severity. RESULTS: 1002 children met criteria for matching (58.9% received CM and 41.1% received PT). In the matched sample of 778 patients, children treated with PT had similar rates of drainage overall (PT: 11.8%, CM: 12.1%; OR 1.44 [OR:0.71-2.94]) and higher rates of drainage associated with growth of any organism (PT: 7.7%, CM: 4.6%; OR 2.41 [95%CI:1.08-5.39]) and Escherichia coli (PT: 4.6%, CM: 1.8%; OR 3.42 [95%CI:1.07-10.92]) compared to treatment with CM. Rates were similar between groups for drainage associated with multiple organisms (PT: 2.6%, CM: 1.5%; OR 3.81 [95%CI:0.96-15.08]) and Pseudomonas (PT: 1.0%, CM: 1.3%; OR 3.42 [95%CI:0.55-21.28]). CONCLUSIONS AND RELEVANCE: Use of antipseudomonal antibiotics is not associated with lower rates of postoperative drainage procedures or more favorable culture profiles in children with complicated appendicitis.

4.
Pediatr Rheumatol Online J ; 21(1): 40, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37098546

RESUMO

BACKGROUND: Antibodies to histone have been associated in the adult literature with systemic lupus erythematosus(SLE) and drug induced lupus(DILE). Little data is available regarding the spectrum of pathology that antibodies to histone encompass in the pediatric population. Prior studies suggest an association with SLE, juvenile idiopathic arthritis(JIA), uveitis and linear scleroderma. METHODS: Patient charts were reviewed that contained positive anti-histone antibody testing during a consecutive three year period. Patient diagnosis along with the presence of: anti-histone antibody titer, ANA, and the presence of other autoantibodies to SSA, SSB, Sm, RNP, dsDNA and chromatin were obtained. The frequency of SLE, JIA and DILE was further investigated in specific subsets. RESULTS: 139 individual charts were reviewed containing 41 different diagnoses. The most common diagnosis was hypermobility arthralgia with 22 patients. The most frequent rheumatologic diagnosis was JIA(nonsystemic) with 19. 13 patients in this study were diagnosed with SLE and 2 with DILE. 18 patients had other autoantibody production, of these, 11 had SLE or DILE. Only one of 62 patients with a weak antihistone antibody titer(1.0-1.5) was diagnosed with SLE. When strong titers are present(> 2.5), the antihistone antibody test was associated with a greater than 50% incidence of an underlying rheumatologic disease and ten times higher incidence of SLE than a weak titer. In regards to the frequency of SLE, there was a statistically significant difference between weak and moderate titers and between weak and strong titers. CONCLUSION: The presence of anti-histone antibody was observed in a variety of diagnoses in the pediatric population. Overall, the presence of anti-histone antibodies appears to have poor diagnostic utility for any specific condition. However, diagnostic utility for SLE does appear to improve with higher titers, when combined with other autoantibody positivity. Strength of titer did not appear to be a factor for JIA, but was the most frequently observed rheumatologic disease in this study.


Assuntos
Artrite Reumatoide , Lúpus Eritematoso Sistêmico , Adulto , Humanos , Criança , Histonas/efeitos adversos , Estudos Retrospectivos , Autoanticorpos , Lúpus Eritematoso Sistêmico/diagnóstico , Anticorpos Antinucleares
5.
JAMA Surg ; 157(8): 685-692, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35648410

RESUMO

Importance: The clinical significance of gangrenous, suppurative, or exudative (GSE) findings is poorly characterized in children with nonperforated appendicitis. Objective: To evaluate whether GSE findings in children with nonperforated appendicitis are associated with increased risk of surgical site infections and resource utilization. Design, Setting, and Participants: This multicenter cohort study used data from the Appendectomy Targeted Database of the American College of Surgeons Pediatric National Surgical Quality Improvement Program, which were augmented with operative report data obtained by supplemental medical record review. Data were obtained from 15 hospitals participating in the Eastern Pediatric Surgery Network (EPSN) research consortium. The study cohort comprised children (aged ≤18 years) with nonperforated appendicitis who underwent appendectomy from July 1, 2015, to June 30, 2020. Exposures: The presence of GSE findings was established through standardized, keyword-based audits of operative reports by EPSN surgeons. Interrater agreement for the presence or absence of GSE findings was evaluated in a random sample of 900 operative reports. Main Outcomes and Measures: The primary outcome was 30-day postoperative surgical site infections (incisional and organ space infections). Secondary outcomes included rates of hospital revisits, postoperative abdominal imaging, and postoperative length of stay. Multivariable mixed-effects regression was used to adjust measures of association for patient characteristics and clustering within hospitals. Results: Among 6133 children with nonperforated appendicitis, 867 (14.1%) had GSE findings identified from operative report review (hospital range, 4.2%-30.2%; P < .001). Reviewers agreed on presence or absence of GSE findings in 93.3% of cases (weighted κ, 0.89; 95% CI, 0.86-0.92). In multivariable analysis, GSE findings were associated with increased odds of any surgical site infection (4.3% vs 2.2%; odds ratio [OR], 1.91; 95% CI, 1.35-2.71; P < .001), organ space infection (2.8% vs 1.1%; OR, 2.18; 95% CI, 1.30-3.67; P = .003), postoperative imaging (5.8% vs 3.7%; OR, 1.70; 95% CI, 1.23-2.36; P = .002), and prolonged mean postoperative length of stay (1.6 vs 0.9 days; rate ratio, 1.43; 95% CI, 1.32-1.54; P < .001). Conclusions and Relevance: In children with nonperforated appendicitis, findings of gangrene, suppuration, or exudate are associated with increased surgical site infections and resource utilization. Further investigation is needed to establish the role and duration of postoperative antibiotics and inpatient management to optimize outcomes in this cohort of children.


Assuntos
Apendicite , Apendicectomia/efeitos adversos , Apendicectomia/métodos , Apendicite/complicações , Apendicite/cirurgia , Criança , Estudos de Coortes , Gangrena/complicações , Humanos , Tempo de Internação , Estudos Retrospectivos , Supuração/complicações , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Resultado do Tratamento
6.
Sensors (Basel) ; 21(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068200

RESUMO

Tropical peatlands such as Ghana's Greater Amanzule peatland are highly valuable ecosystems and under great pressure from anthropogenic land use activities. Accurate measurement of their occurrence and extent is required to facilitate sustainable management. A key challenge, however, is the high cloud cover in the tropics that limits optical remote sensing data acquisition. In this work we combine optical imagery with radar and elevation data to optimise land cover classification for the Greater Amanzule tropical peatland. Sentinel-2, Sentinel-1 and Shuttle Radar Topography Mission (SRTM) imagery were acquired and integrated to drive a machine learning land cover classification using a random forest classifier. Recursive feature elimination was used to optimize high-dimensional and correlated feature space and determine the optimal features for the classification. Six datasets were compared, comprising different combinations of optical, radar and elevation features. Results showed that the best overall accuracy (OA) was found for the integrated Sentinel-2, Sentinel-1 and SRTM dataset (S2+S1+DEM), significantly outperforming all the other classifications with an OA of 94%. Assessment of the sensitivity of land cover classes to image features indicated that elevation and the original Sentinel-1 bands contributed the most to separating tropical peatlands from other land cover types. The integration of more features and the removal of redundant features systematically increased classification accuracy. We estimate Ghana's Greater Amanzule peatland covers 60,187 ha. Our proposed methodological framework contributes a robust workflow for accurate and detailed landscape-scale monitoring of tropical peatlands, while our findings provide timely information critical for the sustainable management of the Greater Amanzule peatland.

7.
Science ; 342(6160): 850-3, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24233722

RESUMO

Quantification of global forest change has been lacking despite the recognized importance of forest ecosystem services. In this study, Earth observation satellite data were used to map global forest loss (2.3 million square kilometers) and gain (0.8 million square kilometers) from 2000 to 2012 at a spatial resolution of 30 meters. The tropics were the only climate domain to exhibit a trend, with forest loss increasing by 2101 square kilometers per year. Brazil's well-documented reduction in deforestation was offset by increasing forest loss in Indonesia, Malaysia, Paraguay, Bolivia, Zambia, Angola, and elsewhere. Intensive forestry practiced within subtropical forests resulted in the highest rates of forest change globally. Boreal forest loss due largely to fire and forestry was second to that in the tropics in absolute and proportional terms. These results depict a globally consistent and locally relevant record of forest change.


Assuntos
Conservação dos Recursos Naturais , Mapeamento Geográfico , Mapas como Assunto , Árvores , Brasil , Indonésia
9.
Appl Environ Microbiol ; 78(23): 8219-26, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23001668

RESUMO

Streptococcus iniae causes severe septicemia and meningitis in farmed fish and is also occasionally zoonotic. Vaccination against S. iniae is problematic, with frequent breakdown of protection in vaccinated fish. The major protective antigens in S. iniae are the polysaccharides of the capsule, which are essential for virulence. Capsular biosynthesis is driven and regulated by a 21-kb operon comprising up to 20 genes. In a long-term study, we have sequenced the capsular operon of strains that have been used in autogenous vaccines across Australia and compared it with the capsular operon sequences of strains subsequently isolated from infected vaccinated fish. Intriguingly, strains isolated from vaccinated fish that subsequently become infected have coding mutations that are confined to a limited number of genes in the cps operon, with the remainder of the genes in the operon remaining stable. Mutations in strains in diseased vaccinated fish occur in key genes in the capsular operon that are associated with polysaccharide configuration (cpsG) and with regulation of biosynthesis (cpsD and cpsE). This, along with high ratios of nonsynonymous to synonymous mutations within the cps genes, suggests that immune response directed predominantly against capsular polysaccharide may be driving evolution in a very specific set of genes in the operon. From these data, it may be possible to design a simple polyvalent vaccine with a greater operational life span than the current monovalent killed bacterins.


Assuntos
Cápsulas Bacterianas/metabolismo , Vias Biossintéticas/genética , Evolução Molecular , Doenças dos Peixes/prevenção & controle , Vacinas Estreptocócicas/administração & dosagem , Streptococcus/genética , Streptococcus/imunologia , Animais , Austrália , Análise Mutacional de DNA , DNA Bacteriano/química , DNA Bacteriano/genética , Doenças dos Peixes/microbiologia , Peixes , Dados de Sequência Molecular , Óperon , Seleção Genética , Análise de Sequência de DNA , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/veterinária , Streptococcus/isolamento & purificação , Streptococcus/metabolismo
10.
Fish Shellfish Immunol ; 31(2): 350-7, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21664976

RESUMO

Genes encoding two hepcidin-like antimicrobial peptides were discovered in Barramundi, Lates calcarifer (barramundi, Giant sea perch). Analysis of the coding regions indicated that genes for each hepcidin comprised 3 exons and 2 introns. The deduced amino acid sequences for each molecule resulted in a protein comprising a signal sequence of 24 aa in each case, coupled to a prepropeptide of 75 aa for hepcidin 1 and 78 aa for hepcidin 2. A cleavage site was identified in each prepropetide at amino acid 64 with the cleavage motif--QKR/QS--resulting in mature peptides of 25 and 28 amino acids respectively. Each mature peptide contained 8 conserved cysteine residues and 3 dimensional modeling predicted a ß-hairpin and ß-sheet structure characteristic of human Liver Expressed Antimicrobial Peptide (LEAP). Analysis of the deduced amino acid sequences by BLAST with phylogenetic supported indicated that hepcidin 1 was a HAMP1-type peptide closely related to hepcidins identified in other Perciformes (Micropterus and Pseudosciaena), whilst hepcidin 2 was a HAMP2-type peptide most similar to a hepcidin previously identified in black rock fish (Sebastes schlegeli). Both hepcidin genes were inducible in barramundi following intraperitoneal injection with lipopolysaccharide, with elevated expression detected in liver and head kidney 3 h post IP injection for hepcidin 1 and in liver only for hepcidin 2. The elevated expression was transient with return to normal levels within 24-48 h. No significant expression of either peptide was detected in spleen, skin or gill following IP injection with LPS.


Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Proteínas de Peixes/genética , Perciformes/genética , Perciformes/imunologia , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/imunologia , Peptídeos Catiônicos Antimicrobianos/metabolismo , Sequência de Bases , DNA Complementar/genética , DNA Complementar/imunologia , DNA Complementar/metabolismo , Proteínas de Peixes/imunologia , Proteínas de Peixes/metabolismo , Perfilação da Expressão Gênica , Hepcidinas , Lipopolissacarídeos/farmacologia , Dados de Sequência Molecular , Perciformes/metabolismo
11.
Cytotechnology ; 63(4): 325-35, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21562973

RESUMO

In the biopharmaceutical industry, adherent growing stem cell cultures gain worldwide importance as cell products. The cultivation process of these cells, such as in stirred tank reactors or in fixed bed reactors, is highly sophisticated. Cultivations need to be monitored and controlled to guarantee product quality and to satisfy GMP requirements. With the process analytical technology (PAT) initiative, requirements regarding process monitoring and control have changed and real-time on-line monitoring tools are recommended. A tool meeting the new requirements may be the dielectric spectroscopy for online viable cell mass determination by measurement of the permittivity. To establish these tools, proper offline methods for data correlation are required. The cell number determination of adherent cells on microcarrier is difficult, as it requires cell detachment from the carrier, which highly increases the statistical error. As an offline method, a fluorescence assay based on SYBR(®)GreenI was developed allowing fast and easy total cell concentration determination without the need to detach the cells from the carrier. The assay is suitable for glass carriers used in stirred tank reactor systems or in fixed bed systems, may be suitable for different cell lines and can be applied to high sample numbers easily. The linear dependency of permittivity to cell concentration of suspended stem cells with the dielectric spectroscopy is shown for even very small cell concentrations. With this offline-method, a correlation of the cell concentration grown on carrier to the permittivity data measured by the dielectric spectroscopy was done successfully.

12.
Biotechnol Adv ; 29(4): 391-401, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21419837

RESUMO

In the biopharmaceutical industry, mammalian and insect cells as well as plant cell cultures are gaining worldwide importance to produce biopharmaceuticals and as products themselves, for example in stem cell therapy. These highly sophisticated cell-based production processes need to be monitored and controlled to guarantee product quality and to satisfy GMP requirements. With the process analytical technology (PAT) initiative, requirements regarding process monitoring and control have changed and real-time in-line monitoring tools are now recommended. Dielectric spectroscopy (DS) can serve as a tool to satisfy some PAT requirements. DS has been used in the medical field for quite some time and it may allow real-time process monitoring of biological cell culture parameters. DS has the potential to enable process optimization, automation, cost reduction, and a more consistent product quality. Dielectric spectroscopy is reviewed here as a tool to monitor biochemical processes. Commercially available dielectric sensing systems are discussed. The potential of this technology is demonstrated through examples of current and potential future applications in research and industry for mammalian and insect cell culture.


Assuntos
Biotecnologia/métodos , Técnicas de Cultura de Células/métodos , Espectroscopia Dielétrica/métodos , Animais , Biomassa , Espectroscopia Dielétrica/instrumentação
13.
Emerg Infect Dis ; 15(12): 1891-6, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19961667

RESUMO

Streptococcus iniae is an emerging zoonotic pathogen; such infections generally occur through injuries associated with preparing whole fresh fish for cooking. Those infected to date have been of Asian descent, are usually elderly (average age 68 years), and have had >/=1 underlying conditions that may predispose them to infection. Studies of the foundations of growth characteristics of S. iniae and its interactions with piscine host cells have recently been complemented by molecular studies. Advances in molecular biology have allowed research groups to identify numerous virulence factors and to explore their roles in the progression of S. iniae infection. Many of these virulence factors are homologous to those found in the major human pathogen S. pyogenes. An increased understanding of the properties of these factors and their effect on the success of infection is leading to novel approaches to control S. iniae infection; in particular, vaccination programs at fish farms have reduced the reservoir of infection for additional clinical cases.


Assuntos
Peixes/microbiologia , Infecções Estreptocócicas/prevenção & controle , Streptococcus/patogenicidade , Adesinas Bacterianas/fisiologia , Animais , Antígenos de Bactérias/fisiologia , Cápsulas Bacterianas/fisiologia , Proteínas da Membrana Bacteriana Externa/fisiologia , Proteínas de Bactérias/fisiologia , Proteínas de Transporte/fisiologia , Eletroforese em Gel de Campo Pulsado , Endopeptidases/fisiologia , Proteínas Hemolisinas/fisiologia , Humanos , Streptococcus/genética , Estreptolisinas/fisiologia , Fatores de Virulência/fisiologia
14.
Appl Environ Microbiol ; 75(9): 2908-19, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19270123

RESUMO

In Streptococcus iniae, lactate metabolism is dependent upon two proteins, lactate permease that mediates uptake and lactate oxidase, a flavin mononucleotide-dependent enzyme that catalyzes oxidation of alpha-hydroxyacids. A novel variant of the lactate oxidase gene, lctO, in Australian isolates of S. iniae from diseased barramundi was found during a diagnostic screen using LOX-1 and LOX-2 primers, yielding amplicons of 920 bp instead of the expected 869 bp. Sequencing of the novel gene variant (type 2) revealed a 51-nucleotide insertion in lctO, resulting in a 17-amino-acid repeat in the gene product, and three-dimensional modeling indicated formation of an extra loop in the monomeric protein structure. The activities of the lactate oxidase enzyme variants expressed in Escherichia coli were examined, indicating that the higher-molecular-weight type 2 enzyme exhibited higher activity. Growth rates of S. iniae expressing the novel type 2 enzyme were not reduced at lactate concentrations of 0.3% and 0.5%, whereas a strain expressing the type 1 enzyme exhibited reduced growth rates at these lactate concentrations. During a retrospective screen of 105 isolates of S. iniae from Australia, the United States, Canada, Israel, Réunion Island, and Thailand, the type 2 variant arose only in isolates from a single marine farm with unusually high tidal flow in the Northern Territory, Australia. Elevated plasma lactate levels in the fish, resulting from the effort of swimming in tidal flows of up to 3 knots, may exert sufficient selective pressure to maintain the novel, high-molecular-weight enzyme variant.


Assuntos
Evolução Molecular , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Perciformes/microbiologia , Streptococcus/enzimologia , Streptococcus/isolamento & purificação , Sequência de Aminoácidos , Animais , Austrália , Canadá , DNA Bacteriano/química , DNA Bacteriano/genética , Escherichia coli/genética , Israel , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Insercional , Estrutura Terciária de Proteína , Sequências Repetitivas de Aminoácidos , Alinhamento de Sequência , Análise de Sequência de DNA , Streptococcus/genética , Tailândia , Estados Unidos
15.
BMC Microbiol ; 8: 67, 2008 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-18430254

RESUMO

BACKGROUND: Binding of serum components by surface M-related proteins, encoded by the emm genes, in streptococci constitutes a major virulence factor in this important group of organisms. The present study demonstrates fibrinogen binding by S. iniae, a Lancefield non-typeable pathogen causing devastating fish losses in the aquaculture industry and an opportunistic pathogen of humans, and identifies the proteins involved and their encoding genes. RESULTS: Fibrinogen binding by S. iniae significantly reduced respiratory burst activity of barramundi peritoneal macrophages in primary cultures compared to BSA-treated or untreated controls, indicating a potentially important role for fibrinogen binding cell-surface proteins in avoiding phagocytic attack in fish. We describe a novel emm-like gene, simA, encoding a 57 kDa fibrinogen binding M-like protein in S. iniae. These SiM proteins and their corresponding tetrameric structures from some sequevar types (approximately 230 kDa) bound fibrinogen in Western blots. simA was most closely related (32% identity) to the demA gene of S. dysgalactiae. Genome walking and sequencing determined the genetic organization of the simA region had similarities to the mgrC regulon in GCS and to S. uberis. Moreover, a putative multigene regulator, mgx was orientated in the opposite direction to the simA gene in common with S. uberis, but contrary to findings in GAS and GCS. In GAS, diversity among emm-genes and consequent diversity of their M-related proteins results in substantial antigenic variation. However, an extensive survey of S. iniae isolates from diverse geographic regions and hosts revealed only three variants of the gene, with one sequevar accounting for all but two of the 50 isolates analysed. CONCLUSION: These proteins play a role in avoiding oxidative attack by phagocytic cells during infection of fish by S. iniae, but genetic diversity amongst these key surface proteins has not yet arisen. This lack of diversity coupled with a functional role in macrophage resistance suggests that these proteins may constitute important targets for future vaccines against S. iniae in fish.


Assuntos
Antígenos de Bactérias/genética , Antígenos de Bactérias/metabolismo , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Fibrinogênio/genética , Fibrinogênio/metabolismo , Streptococcus/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Células Cultivadas , Ordem dos Genes , Genes Bacterianos , Variação Genética , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/microbiologia , Dados de Sequência Molecular , Perciformes/metabolismo , Perciformes/microbiologia , Ligação Proteica , Explosão Respiratória
16.
J Mol Evol ; 52(3): 232-8, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11428460

RESUMO

Friedreich ataxia is an autosomal recessive neurodegenerative disorder associated with a GAA repeat expansion in the first intron of the gene (FRDA) encoding a novel, highly conserved, 210 amino acid protein known as frataxin. Normal variation in repeat size was determined by analysis of more than 600 DNA samples from seven human populations. This analysis showed that the most frequent allele had nine GAA repeats, and no alleles with fewer than five GAA repeats were found. The European and Syrian populations had the highest percentage of alleles with 10 or more GAA repeats, while the Papua New Guinea population did not have any alleles carrying more than 10 GAA repeats. The distributions of repeat sizes in the European, Syrian, and African American populations were significantly different from those in the Asian and Papua New Guinea populations (p < 0.001). The GAA repeat size was also determined in five nonhuman primates. Samples from 10 chimpanzees, 3 orangutans, 1 gorilla, 1 rhesus macaque, 1 mangabey, and 1 tamarin were analyzed. Among those primates belonging to the Pongidae family, the chimpanzees were found to carry three or four GAA repeats, the orangutans had four or five GAA repeats, and the gorilla carried three GAA repeats. In primates belonging to the Cercopithecidae family, three GAA repeats were found in the mangabey and two in the rhesus macaque. However, an AluY subfamily member inserted in the poly(A) tract preceding the GAA repeat region in the rhesus macaque, making the amplified sequence approximately 300 bp longer. The GAA repeat was also found in the tamarin, suggesting that it arose at least 40 million years ago and remained relatively small throughout the majority of primate evolution, with a punctuated expansion in the human genome.


Assuntos
Ataxia de Friedreich/genética , Variação Genética , Filogenia , Repetições de Trinucleotídeos/genética , Alelos , Animais , Sequência de Bases , Cercocebus atys/genética , Evolução Molecular , Hominidae/genética , Humanos , Macaca mulatta/genética , Dados de Sequência Molecular , Primatas/genética , Saguinus/genética , Alinhamento de Sequência
17.
Ambio ; 30(6): 351-5, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11757283

RESUMO

Joint Implementation under the Climate Change Convention and Clean Development Mechanism of the Kyoto Protocol require a scientific understanding of current carbon stocks, fluxes, and sequestration potential, especially in tropical ecosystems where there are large carbon reservoirs, significant carbon emissions, and large land areas available for reforestation. Central Africa contains 10% of the world's remaining tropical moist forests and has received little attention in carbon studies. In 1980, above-ground carbon stocks in the central African ecosystem were 28.92 Pg and were reduced to 24.79 Pg by 1990. Improved forest management aimed at increasing biomass density could sequester 18.32 Pg of carbon, and over 500,000 km2 formerly forested land will be available by 2050 for reforestation with a capacity to offset 10 Pg carbon. Understanding the spatial distribution of biomass carbon and sequestration potential will be essential for carbon trading initiatives through Joint Implementation and Clean Development Mechanism.


Assuntos
Carbono , Efeito Estufa , Árvores , África , Ecossistema , Monitoramento Ambiental , Clima Tropical
18.
Genet Epidemiol ; 21 Suppl 1: S794-9, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11793780

RESUMO

An extension of the traditional regression of offspring on midparent (ROMP) method was used to estimate the heritability of the trait, test for marker association, and estimate the heritability attributable to a marker locus. The fifty replicates of the Genetic Analysis Workshop (GAW) 12 simulated general population data were used to compare the ROMP method with the variance components method as implemented in SOLAR as a test for marker association, and to a standard analysis of variance (ANOVA) method. Large sample statistical properties of the ROMP and ANOVA methods were compared using 2,000 replicates resampled from the families of the original 50 replicates. Overall, the power to detect a completely associated single nucleotide polymorphism (SNP) marker was high, and the type I error rates were similar to nominal significance levels for all three methods. The standard deviations of the estimates of the heritability of the trait were large for both SOLAR and ROMP, but the estimates were, on average, close to those of the generating model for both methods. However, on average, SOLAR overestimated the heritability attributable to the associated SNP marker (by 256%) while ROMP underestimated it (by 26%).


Assuntos
Mapeamento Cromossômico/estatística & dados numéricos , Marcadores Genéticos/genética , Predisposição Genética para Doença/genética , Modelos Genéticos , Polimorfismo de Nucleotídeo Único/genética , Análise de Variância , Testes Genéticos , Genética Populacional , Genótipo , Humanos , Fenótipo , Análise de Regressão
19.
Br J Psychol ; 91 ( Pt 2): 189-202, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10832514

RESUMO

Two experiments demonstrate that post-event information, when delivered by another person, can affect people's memory reports. In the first experiment participants were shown several cars, and later, in pairs, given an 'old'/'new' recognition test on these cars plus several lures. There was a small but reliable effect of memory conformity. When the person was given misinformation this lowered accuracy, while presenting accurate information increased accuracy. In the second experiment participants, in pairs, viewed an identical crime except that half saw an accomplice with the thief and half did not. Initial memories were very accurate, but after discussing the crime with the other person in the pair (who saw a slightly different sequence), most pairs conformed. Confidence ratings strongly predicted which person in the pair persuaded the other. Parallels with eyewitness testimony in the Oklahoma bombing case and implications for police interviewing more generally are discussed.


Assuntos
Rememoração Mental , Conformidade Social , Adulto , Análise de Variância , Crime , Inglaterra , Feminino , Humanos , Modelos Logísticos , Masculino , Sensibilidade e Especificidade
20.
Toxicol Pathol ; 27(3): 370-9, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10356716

RESUMO

Hematology and serum chemistry parameters were analyzed in 2 groups of pregnant rabbits to assess changes in these parameters over the course of gestation. These data were used to generate a historical control reference range for embryofetal development regulatory toxicology studies. During the 28-day gestation period, the following major changes were observed. Red blood cell counts, hemoglobin, and hematocrit increased slightly up to day 13 and subsequently decreased progressively to a nadir for all parameters on day 25. Reticulocyte counts increased maximally by day 16 and then decreased to a minimum value on day 28. White blood cell counts progressively declined after day 7. Platelet counts increased slightly by day 10, were relatively stable until day 13, then progressively decreased to a nadir on day 25. Aspartate aminotransferase and alanine aminotransferease values increased steadily throughout the study to reach a maximum value on day 25. Triglycerides increased to their maximum value by day 19 and then steadily decreased until day 28, whereas cholesterol decreased progressively to reach a nadir on day 25. Urea and total protein decreased steadily from day 13 onward. Calcium values decreased throughout the study to reach a minimum value on day 28. Phosphorus values increased slightly on days 7 and 13 and then progressively decreased to reach a nadir on day 28. With a few exceptions, changes that occur in clinical pathology parameters during pregnancy in the rabbit are similar to those observed in pregnant women. Therefore, the rabbit can be considered a suitable species for embryofetal development toxicity studies with regard to clinical pathology.


Assuntos
Prenhez/fisiologia , Coelhos/fisiologia , Animais , Testes de Química Clínica , Desenvolvimento Embrionário e Fetal/fisiologia , Feminino , Testes Hematológicos , Tamanho da Ninhada de Vivíparos , Gravidez , Valores de Referência , Testes de Toxicidade/métodos
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