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2.
Phys Chem Chem Phys ; 24(38): 23884-23892, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36165463

RESUMO

Gold-based catalysts have received tremendous attention as supports and nanoparticles for heterogeneous catalysis, in part due to the ability of nanoscale Au to catalyze reactions at low temperatures in oxidative environments. Surface defects are known active sites for low temperature Au chemistry, so a full understanding of the interplay between intermolecular interactions and surface morphology is essential to an advanced understanding of catalytic behavior and efficiency. In a systematic study to better understand the adsorption and intermolecular behavior of small alcohols (C1-C4) on Au(111) defect sites, coverage studies of methanol, ethanol, 1-propanol, 1-butanol, 2-butanol, and isobutanol have been conducted on Au(111) using ultrahigh vacuum temperature programmed desorption (UHV-TPD). These small alcohols molecularly adsorb on the Au(111) surface and high resolution experiments reveal distinct terrace, step edge, and kink adsorption features for each molecule. The hydrogen-bonded (H-bonded) networks of small alcohols on Au(111), except for 1-butanol and isobutanol, have been previously imaged on the molecular level at low temperatures by scanning tunneling microscopy. Primary C1-C3 alcohols exhibit planar H-bonded long extended zigzag chain networks while 2-butanol arranges in tetramer clusters of H-bonded molecules due to steric hindrance inhibiting the proximity of molecules on Au(111). Herein, the desorption energy of small primary alcohols was shown to trend linearly with increasing C1-C4 carbon chain length, indicating that the H-bonded molecular packing of 1-butanol resembles that of methanol, ethanol, and 1-propanol, while isobutanol and 2-butanol deviate from the trend. Butanol isomer studies allow the prediction of isobutanol long extended chains in contrast to tetramers. The distinction between the desorption of butanol isomers highlights the role of intermolecular interactions due to the difference in molecular packing structures on Au(111). Furthermore, by studying the energetics of terrace H-bonded networks in comparison with molecular adsorption at undercoordinated step edge and kink defect sites, it is shown that the contribution of stabilizing van der Waals forces to the overall adsorption energy is less for small alcohols adsorbed at kink sites (3.1 kJ mol-1 per CH2) and similar for those adsorbed at step edge (4.8 kJ mol-1 per CH2) and Au terrace sites (4.9 kJ mol-1 per CH2).

3.
Sci Rep ; 12(1): 13574, 2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35945451

RESUMO

The propolis industry is well established in European, South American and East Asian countries. Within Australia, this industry is beginning to emerge with a few small-scale producers. To contribute to the development of the Australian propolis industry, the present study aimed to examine the quality and chemical diversity of propolis collected from various regions across Australia. The results of testing 158 samples indicated that Australian propolis had pure resin yielding from 2 to 81% by weight, total phenolic content and total flavonoid content in one gram of dry extract ranging from a few up to 181 mg of gallic acid equivalent and 145 mg of quercetin equivalent, respectively. Some Australian propolis showed more potent antioxidant activity than the well-known Brazilian green, Brazilian red, and Uruguayan and New Zealand poplar-type propolis in an in vitro DPPH assay. In addition, an HPLC-UV analysis resulted in the identification of 16 Australian propolis types which can be considered as high-grade propolis owing to their high total phenolic content. Chemometric analysis of their 1H NMR spectra revealed that propolis originating from the eastern and western coasts of Australia could be significantly discriminated based on their chemical composition.


Assuntos
Própole , Animais , Antioxidantes/análise , Austrália , Abelhas , Cromatografia Líquida de Alta Pressão , Flavonoides/química , Fenóis/análise , Própole/química
4.
MAbs ; 13(1): 2000348, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34781834

RESUMO

Advances in antibody discovery technologies, especially with the availability of humanized mice and phage/yeast library approaches, enable the generation of a large diversity of antibodies against nearly any target of interest. As a result, there is an increasing demand for the production of larger numbers of purified antibodies at quantities (10s-100s of milligrams) sufficient for functional screening assays, drug-ability/develop-ability studies and immunogenicity assessments. To accommodate this need, new methods are required that bridge miniature high throughput/plate-based purification and conventional, one at a time, two-step purification at much larger scales. Thus, we developed a semi-automated, mid-scale (i.e., 1-75 mg) purification process that uses a combination of parallel affinity capture and automated sequential polishing to provide substantially improved throughput while delivering high purity. We optimized the affinity capture step to perform 24 monoclonal antibody purifications in parallel using a Protein Maker for 20-200 mL culture media. The eluant is transferred directly to an AKTA pure system equipped with an autosampler for sequential preparative size exclusion chromatography to remove aggregates and undesirable impurities, as well as exchange the antibody into a buffer suitable for most uses, including cell-based assays. This two-step purification procedure, together with plate-based protein analytical methods, can purify 24-48 monoclonal antibodies in <20 hours and generate up to 80 mg per sample. A stringent clean-in-place protocol for both systems and column maintenance was designed and established to minimize endotoxin contamination. This process has proven to be very reliable and robust, enabling the production of thousands of antibodies of sufficient quality and quantity that are suitable for cell-based assays, biochemical/biophysical characterization, and in vivo animal models.


Assuntos
Anticorpos Monoclonais , Proteína Estafilocócica A , Animais , Anticorpos Monoclonais/química , Cromatografia de Afinidade/métodos , Cromatografia em Gel , Camundongos , Proteína Estafilocócica A/química
5.
J Speech Lang Hear Res ; 64(2): 491-509, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33472006

RESUMO

Purpose As follow-up to a previous study of probes, we evaluated the marking of tense and agreement (T/A) in language samples by children with specific language impairment (SLI) and typically developing controls in African American English (AAE) and Southern White English (SWE) while also examining the clinical utility of different scoring approaches and cut scores across structures. Method The samples came from 70 AAE- and 36 SWE-speaking kindergartners, evenly divided between the SLI and typically developing groups. The structures were past tense, verbal -s, auxiliary BE present, and auxiliary BE past. The scoring approaches were unmodified, modified, and strategic; these approaches varied in the scoring of forms classified as nonmainstream and other. The cut scores were dialect-universal and dialect-specific. Results Although low numbers of some forms limited the analyses, the results generally supported those previously found for the probes. The children produced a large and diverse inventory of mainstream and nonmainstream T/A forms within the samples; strategic scoring led to the greatest differences between the clinical groups while reducing effects of the children's dialects; and dialect-specific cut scores resulted in better clinical classification accuracies, with measures of past tense leading to the highest levels of classification accuracy. Conclusions For children with SLI, the findings contribute to studies that call for a paradigm shift in how children's T/A deficits are assessed and treated across dialects. A comparison of findings from the samples and probes indicates that probes may be the better task for identifying T/A deficits in children with SLI in AAE and SWE. Supplemental Material https://doi.org/10.23641/asha.13564709.


Assuntos
Idioma , Transtorno Específico de Linguagem , Negro ou Afro-Americano , Criança , Linguagem Infantil , Humanos , Testes de Linguagem , População Branca
6.
J Speech Lang Hear Res ; 62(9): 3443-3461, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31525131

RESUMO

Purpose In African American English and Southern White English, we examined whether children with specific language impairment (SLI) overtly mark tense and agreement structures at lower percentages than typically developing (TD) controls, while also examining the effects of dialect, structure, and scoring approach. Method One hundred six kindergartners completed 4 dialect-informed probes targeting 8 tense and agreement structures. The 3 scoring approaches varied in the treatment of nonmainstream English forms and responses coded as Other (i.e., those not obligating the target structure). The unmodified approach counted as correct only mainstream overt forms out of all responses, the modified approach counted as correct all mainstream and nonmainstream overt forms and zero forms out of all responses, and the strategic approach counted as correct all mainstream and nonmainstream overt forms out of all responses except those coded as Other. Results With the probes combined and separated, the unmodified and strategic scoring approaches showed lower percentages of overt marking by the SLI groups than by the TD groups; this was not always the case for the modified scoring approach. With strategic scoring and dialect-specific cut scores, classification accuracy (SLI vs. TD) was highest for the 8 individual structures considered together, the past tense probe, and the past tense probe irregular items. Dialect and structure effects and dialect differences in classification accuracy also existed. Conclusions African American English- and Southern White English-speaking kindergartners with SLI overtly mark tense and agreement at lower percentages than same dialect-speaking TD controls. Strategic scoring of dialect-informed probes targeting tense and agreement should be pursued in research and clinical practice.


Assuntos
Negro ou Afro-Americano , Linguagem Infantil , Linguística , Transtorno Específico de Linguagem , População Branca , Criança , Pré-Escolar , Humanos , Louisiana
7.
PM R ; 10(4): 357-364, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28919499

RESUMO

BACKGROUND: Ultrasound guidance is increasingly being used for neurolytic procedures that have traditionally been done with electrical stimulation (e-stim) guidance alone. Ultrasound visualization with e-stim-guided neurolysis can potentially allow adjustments in injection protocols that will reduce the volume of neurolytic agent needed to achieve clinical improvement. OBJECTIVE: This study compared e-stim only to e-stim with ultrasound guidance in phenol neurolysis of the musculocutaneous nerve (MCN) for elbow flexor spasticity. We also evaluated the ultrasound appearance of the MCN in this population. DESIGN: Retrospective review. SETTING: University hospital outpatient clinic. PARTICIPANTS: Adults (N = 167) receiving phenol neurolysis to the MCN for treatment of elbow flexor spasticity between 1997 and 2014 and adult control subjects. METHODS: For each phenol injection of the MCN, the method of guidance, volume of phenol injected, technical success, improved range of motion at the elbow postinjection, adverse effects, reason for termination of injections, and details of concomitant botulinum toxin injection were recorded. The ultrasound appearance of the MCN, including nerve cross-sectional area and shape, were recorded and compared between groups. MAIN OUTCOME MEASURES: The volume of phenol injected and MCN cross-sectional area and shape as demonstrated by ultrasound. RESULTS: The addition of ultrasound to e-stim-guided phenol neurolysis was associated with lower doses of phenol when compared to e-stim guidance alone (2.31 mL versus 3.69 mL, P < .001). With subsequent injections, the dose of phenol increased with e-stim guidance (P < .001), but not with e-stim and ultrasound guidance (P = .95). Both methods of guidance had high technical success, improved ROM at elbow postinjection, and low rates of adverse events. In comparing the ultrasound appearance of the MCN in patients with spasticity to that of normal controls, there was no difference in the cross-sectional area of the nerve, but there was more variability in shape. CONCLUSIONS: Combined e-stim and ultrasound guidance during phenol neurolysis to the MCN allows a smaller volume of phenol to be used for equal effect, both at initial and repeat injection. The MCN shape was more variable in individuals with spasticity; this should be recognized so as to successfully locate the nerve to perform neurolysis. LEVEL OF EVIDENCE: IV.


Assuntos
Estimulação Elétrica/métodos , Espasticidade Muscular/terapia , Nervo Musculocutâneo/fisiopatologia , Bloqueio Nervoso/métodos , Fenol/farmacologia , Ultrassonografia/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/fisiopatologia , Nervo Musculocutâneo/diagnóstico por imagem , Nervo Musculocutâneo/efeitos dos fármacos , Estudos Retrospectivos , Soluções Esclerosantes/farmacologia , Resultado do Tratamento
8.
J Speech Lang Hear Res ; 60(9): 2557-2568, 2017 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-28796859

RESUMO

Purpose: We compared copula and auxiliary verb BE use by African American English-speaking children with and without a creole heritage, using Gullah/Geechee as the creole criterion, to determine if differences exist, the nature of the differences, and the impact of the differences on interpretations of ability. Method: Data came from 38 children, aged 5 to 6 years (19 with Gullah/Geechee and 19 without Gullah/Geechee heritage). All were developing language typically, with groups matched on gender, maternal education, and, when possible, test scores. The children's productions of BE were elicited using a screener, probes, and language samples. Results: Although many similarities were documented, the 2 groups' BE systems differed in 3 ways: use of unique forms (i.e., də), unique use of shared forms (i.e., BEEN), and rates of use of shared forms (e.g., am, is, was/were, was for were). Although most noticeable in the language samples, differences surfaced across tasks and showed the potential to affect interpretations of ability. Conclusions: Dialect variation that is tied to children's creole heritage exists, involves 3 types of variation, and potentially affects interpretations of ability. Effects of a heritage language and different types of variation should be considered in research and clinical endeavors with African American English-speaking children.


Assuntos
Negro ou Afro-Americano/psicologia , Linguagem Infantil , Linguística , Criança , Pré-Escolar , Cultura , Feminino , Humanos , Masculino
9.
J Pediatric Infect Dis Soc ; 6(4): 366-375, 2017 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-28339623

RESUMO

OBJECTIVE: In this report, we aim to describe the epidemiology of extended-spectrum cephalosporin-resistant (ESC-R) and carbapenem-resistant (CR) Enterobacteriaceae infections in children. METHODS: ESC-R and CR Enterobacteriaceae isolates from normally sterile sites of patients aged <22 years from 4 freestanding pediatric medical centers were collected along with the associated clinical data. RESULTS: The overall frequencies of ESC-R and CR isolates according to hospital over the 4-year study period ranged from 0.7% to 2.8%. Rates of ESC-R or CR Escherichia coli and Klebsiella pneumoniae varied according to hospital and ranged from 0.75 to 3.41 resistant isolates per 100 isolates (P < .001 for any differences). E coli accounted for 272 (77%) of the resistant isolates; however, a higher rate of resistance was observed in K pneumoniae isolates (1.78 vs 1.27 resistant isolates per 100 same-species isolates, respectively; P = .005). One-third of the infections caused by ESC-R or CR E coli were community-associated. In contrast, infections caused by ESC-R or CR K pneumoniae were more likely than those caused by resistant E coli to be healthcare- or hospital-associated and to occur in patients with an indwelling device (P ≤ .003 for any differences, multivariable logistic regression). Nonsusceptibility to 3 common non-ß-lactam agents (ciprofloxacin, gentamicin, and trimethoprim-sulfamethoxazole) occurred in 23% of the ESC-R isolates. The sequence type 131-associated fumC/fimH-type 40-30 was the most prevalent sequence type among all resistant E coli isolates (30%), and the clonal group 258-associated allele tonB79 was the most prevalent allele among all resistant K pneumoniae isolates (10%). CONCLUSIONS: The epidemiology of ESC-R and CR Enterobacteriaceae varied according to hospital and species (E coli vs K pneumoniae). Both community and hospital settings should be considered in future research addressing pediatric ESC-R Enterobacteriaceae infection.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecção Hospitalar/epidemiologia , Infecções por Enterobacteriaceae/epidemiologia , Hospitais Pediátricos/estatística & dados numéricos , Adolescente , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Resistência às Cefalosporinas , Criança , Pré-Escolar , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Masculino , Epidemiologia Molecular , Estados Unidos/epidemiologia , Adulto Jovem
10.
Pathogens ; 4(4): 708-21, 2015 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-26506394

RESUMO

Staphylococcus aureus are Gram-positive bacteria that are the leading cause of recurrent infections in humans that include pneumonia, bacteremia, osteomyelitis, arthritis, endocarditis, and toxic shock syndrome. The emergence of methicillin resistant S. aureus strains (MRSA) has imposed a significant concern in sustained measures of treatment against these infections. Recently, MRSA strains deficient in expression of a serine/threonine kinase (Stk1 or PknB) were described to exhibit increased sensitivity to ß-lactam antibiotics. In this study, we screened a library consisting of 280 drug-like, low-molecular-weight compounds with the ability to inhibit protein kinases for those that increased the sensitivity of wild-type MRSA to ß-lactams and then evaluated their toxicity in mice. We report the identification of four kinase inhibitors, the sulfonamides ST085384, ST085404, ST085405, and ST085399 that increased sensitivity of WT MRSA to sub-lethal concentrations of ß-lactams. Furthermore, these inhibitors lacked alerting structures commonly associated with toxic effects, and toxicity was not observed with ST085384 or ST085405 in vivo in a murine model. These results suggest that kinase inhibitors may be useful in therapeutic strategies against MRSA infections.

11.
Psychol Sci ; 26(12): 1965-71, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26502746

RESUMO

When speakers selectively retrieve previously learned information, listeners often concurrently, and covertly, retrieve their memories of that information. This concurrent retrieval typically enhances memory for mentioned information (the rehearsal effect) and impairs memory for unmentioned but related information (socially shared retrieval-induced forgetting, SSRIF), relative to memory for unmentioned and unrelated information. Building on research showing that anxiety leads to increased attention to threat-relevant information, we explored whether concurrent retrieval is facilitated in high-anxiety real-world contexts. Participants first learned category-exemplar facts about meningococcal disease. Following a manipulation of perceived risk of infection (low vs. high risk), they listened to a mock radio show in which some of the facts were selectively practiced. Final recall tests showed that the rehearsal effect was equivalent between the two risk conditions, but SSRIF was significantly larger in the high-risk than in the low-risk condition. Thus, the tendency to exaggerate consequences of news events was found to have deleterious consequences.


Assuntos
Atenção , Cognição , Rememoração Mental , Medição de Risco , Comportamento Social , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Infect Immun ; 83(3): 1078-88, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25561709

RESUMO

Group B streptococci (GBS; Streptococcus agalactiae) are beta-hemolytic, Gram-positive bacteria that are common asymptomatic colonizers of healthy adults. However, these opportunistic bacteria also cause invasive infections in human newborns and in certain adult populations. To adapt to the various environments encountered during its disease cycle, GBS encodes a number of two-component signaling systems. Previous studies have indicated that the TCS comprising the sensor histidine kinase RgfC and the response regulator RgfA mediate GBS binding to extracellular matrix components, such as fibrinogen. However, in certain GBS clinical isolates, a point mutation in rgfA results in premature truncation of the response regulator. The truncated RgfA protein lacks the C-terminal DNA binding domain necessary for promoter binding and gene regulation. Here, we show that deletion of rgfC in GBS strains lacking a functional RgfA increased systemic infection. Furthermore, infection with the rgfC mutant increased induction of proinflammatory signaling pathways in vivo. Phosphoproteomic analysis revealed that 19 phosphopeptides corresponding to 12 proteins were differentially phosphorylated at aspartate, cysteine, serine, threonine, or tyrosine residues in the rgfC mutant. This included aspartate phosphorylation of a tyrosine kinase, CpsD, and a transcriptional regulator. Consistent with this observation, microarray analysis of the rgfC mutant indicated that >200 genes showed altered expression compared to the isogenic wild-type strain and included transcriptional regulators, transporters, and genes previously associated with GBS pathogenesis. Our observations suggest that in the absence of RgfA, nonspecific RgfC signaling affects the expression of virulence factors and GBS pathogenesis.


Assuntos
Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica , Proteínas Quinases/genética , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/genética , Streptococcus agalactiae/patogenicidade , Sequência de Aminoácidos , Animais , Proteínas de Bactérias/metabolismo , Encéfalo/metabolismo , Encéfalo/microbiologia , Encéfalo/patologia , Linhagem Celular , Células Endoteliais/metabolismo , Células Endoteliais/microbiologia , Células Endoteliais/patologia , Perfilação da Expressão Gênica , Histidina Quinase , Humanos , Masculino , Camundongos , Camundongos Endogâmicos , Dados de Sequência Molecular , Mutação , Fosforilação , Regiões Promotoras Genéticas , Proteínas Quinases/metabolismo , Alinhamento de Sequência , Transdução de Sinais , Infecções Estreptocócicas/patologia , Streptococcus agalactiae/metabolismo , Transcrição Gênica , Virulência
13.
Diagn Microbiol Infect Dis ; 80(1): 87-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25041704

RESUMO

Multidrug-resistant (MDR) Enterobacteriaceae infections are associated with increased morbidity. We describe a 20-year-old hematopoietic cell transplantation recipient with recurrent MDR Klebsiella pneumoniae infection, prolonged intestinal colonization, and subsequent intestinal decontamination. Further study should evaluate stool surveillance, molecular typing, and fecal microbiota transplantation for patients with intestinal MDR Enterobacteriaceae carriage.


Assuntos
Antibacterianos/administração & dosagem , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Adulto , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Farmacorresistência Bacteriana Múltipla , Fezes/microbiologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Hospedeiro Imunocomprometido , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/genética , Masculino , Recidiva , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/microbiologia , Transplantados , Adulto Jovem
14.
Antimicrob Agents Chemother ; 58(7): 3997-4004, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24798269

RESUMO

The objective of this study is to describe the epidemiology of intestinal carriage with extended-spectrum-cephalosporin-resistant Enterobacteriaceae in children with index infections with these organisms. Patients with resistant Escherichia coli or Klebsiella bacteria isolated from the urine or a normally sterile site between January 2006 and December 2010 were included in this study. Available infection and stool isolates underwent phenotypic and molecular characterization. Clinical data relevant to the infections were collected and analyzed. Overall, 105 patients were identified with 106 extended-spectrum-cephalosporin-resistant E. coli (n = 92) or Klebsiella (n = 14) strains isolated from urine or a sterile site. Among the 27 patients who also had stool screening for resistant Enterobacteriaceae, 17 (63%) had intestinal carriage lasting a median of 199 days (range, 62 to 1,576). There were no significant differences in demographic, clinical, and microbiological variables between those with and those without intestinal carriage. Eighteen (17%) patients had 37 subsequent resistant Enterobacteriaceae infections identified: 31 urine and 6 blood. In a multivariable analysis, antibiotic intake in the 91 days prior to subsequent urine culture was significantly associated with subsequent urinary tract infection with a resistant organism (hazard ratio, 14.3; 95% confidence interval [CI], 1.6 to 130.6). Intestinal carriage and reinfection were most commonly due to bacterial strains of the same sequence type and with the same resistance determinants as the index extended-spectrum-cephalosporin-resistant Enterobacteriaceae, but carriage and reinfection with different resistant Enterobacteriaceae strains also occurred.


Assuntos
Antibacterianos/uso terapêutico , Portador Sadio/tratamento farmacológico , Portador Sadio/microbiologia , Cefalosporinas/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Adolescente , Criança , Pré-Escolar , DNA Bacteriano/genética , Farmacorresistência Bacteriana , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Fezes/microbiologia , Feminino , Genótipo , Humanos , Lactente , Intestinos/microbiologia , Masculino , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , Fatores de Risco , beta-Lactamases/biossíntese , beta-Lactamases/genética
15.
Pediatr Dev Pathol ; 17(2): 75-84, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24555441

RESUMO

Recurrent genetic alterations found in hepatic mesenchymal hamartoma include either androgenetic-biparental mosaicism or chromosomal rearrangements involving chromosome 19q13.4, in the vicinity of the chromosome 19q microRNA cluster (C19MC). Abnormal activation of C19MC, which is subject to paternal imprinting and is normally expressed only in placenta, could account for both genetic associations because androgenetic cells carry only paternal chromosomes. In this study, a 4.2-Mb deletion involving the 5'-end of C19MC was detected in a sporadic mesenchymal hamartoma by chromosomal microarray. Fluorescence in situ hybridization studies showed that the deletion localized to mesenchymal cells in the stroma of the hamartoma. Quantitative real-time polymerase chain reaction analysis of this tumor, 9 other sporadic hepatic mesenchymal hamartomas, and 3 hamartomas associated with androgenetic-biparental mosaicism demonstrated C19MC microRNA expression in all but 2 sporadic cases, with no significant expression in control liver. The findings support a pathogenetic model for mesenchymal hamartoma as a consequence of "ectopic" activation of C19MC in hepatic stroma, due to either chromosomal rearrangements or paternal uniparental disomy.


Assuntos
Cromossomos Humanos Par 19/genética , Predisposição Genética para Doença/genética , Hamartoma/genética , Hepatopatias/genética , MicroRNAs/genética , Mosaicismo , Adolescente , Criança , Pré-Escolar , Aberrações Cromossômicas , Cromossomos Humanos Par 19/metabolismo , Feminino , Testes Genéticos/métodos , Hamartoma/metabolismo , Hamartoma/patologia , Humanos , Lactente , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , MicroRNAs/metabolismo , Família Multigênica , Placenta/metabolismo , Placenta/patologia , Gravidez
16.
Antimicrob Agents Chemother ; 56(11): 5971-81, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22964251

RESUMO

Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients undergo remarkable phenotypic divergence over time, including loss of pigmentation, hemolysis, motility, and quorum sensing and emergence of antibiotic hypersusceptibility and/or auxotrophism. With prolonged antibiotic treatment and steady decline in lung function in chronically infected patients, the divergent characteristics associated with CF isolates have traditionally been regarded as "adapted/unusual virulence," despite the degenerative nature of these adaptations. We examined the phenotypic and genotypic diversity in clonally related isogenic strains of P. aeruginosa from individual CF patients. Our observations support a novel model of intra-airway pseudomonal syntrophy and accompanying loss of virulence. A 2007 calendar year collection of CF P. aeruginosa isolates (n = 525) from 103 CF patients yielded in vitro MICs of sulfamethoxazole-trimethoprim (SMX-TMP, which typically has no activity against P. aeruginosa) ranging from 0.02 to >32 µg/ml (median, 1.5). Coisolation of clonally related SMX-TMP-susceptible and -resistant P. aeruginosa strains from the same host was common (57%), as were isogenic coisolates with mutations in efflux gene determinants (mexR, mexAB-oprM, and mexZ) and genes governing DNA mismatch repair (mutL and mutS). In this cohort, complete in vitro growth complementation between auxotrophic and prototrophic P. aeruginosa isogenic strains was evident and concurrent with the coding sequence mosaicism in resistance determinants. These observations suggest that syntrophic clonal strains evolve in situ in an organized colonial structure. We propose that P. aeruginosa adopts a multicellular lifestyle in CF patients due to host selection of an energetically favorable, less-virulent microbe restricted within and symbiotic with the airway over the host's lifetime.


Assuntos
Adaptação Fisiológica/genética , Fibrose Cística/microbiologia , Genes Bacterianos , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Sistema Respiratório/microbiologia , Adaptação Fisiológica/efeitos dos fármacos , Antibacterianos/farmacologia , Doença Crônica , Células Clonais , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Heterogeneidade Genética , Humanos , Testes de Sensibilidade Microbiana , Mosaicismo , Mutação , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/classificação , Pseudomonas aeruginosa/isolamento & purificação , Sistema Respiratório/efeitos dos fármacos , Combinação Trimetoprima e Sulfametoxazol/farmacologia
17.
Infect Drug Resist ; 5: 75-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22573939

RESUMO

Chlorhexidine gluconate (CHG) is a topical antiseptic used in a myriad of clinical settings. Recently, CHG baths have been shown to decrease multidrug-resistant organism acquisition and infections and catheter-associated bloodstream infections. The present study examined the effects of daily bathing with CHG on the recovery and antimicrobial susceptibility of cultivable cutaneous bacteria. The objectives of this study were to (1) explore the effects of clinical CHG bathing on cultivable cutaneous bacteria, (2) study the relationship between CHG minimum inhibitory concentration and antimicrobial susceptibility of coagulase-negative staphylococci, and (3) demonstrate the feasibility of the approach so a more definitive study may be performed. Significant decreases in bacterial colony counts and phenotypic diversity occurred with greater CHG exposure. The findings also suggest an inverse relationship between CHG minimum inhibitory concentration and antimicrobial susceptibility. Larger prospective studies are necessary to fully investigate the clinical impact of CHG usage.

18.
Immunogenetics ; 64(6): 421-34, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22322672

RESUMO

The SIV-infected rhesus macaque (Macaca mulatta) is the most established model of AIDS disease systems, providing insight into pathogenesis and a model system for testing novel vaccines. The understanding of cellular immune responses based on the identification and study of Major Histocompatibility Complex (MHC) molecules, including their MHC:peptide-binding motif, provides valuable information to decipher outcomes of infection and vaccine efficacy. Detailed characterization of Mamu-B*039:01, a common allele expressed in Chinese rhesus macaques, revealed a unique MHC:peptide-binding preference consisting of glycine at the second position. Peptides containing a glycine at the second position were shown to be antigenic from animals positive for Mamu-B*039:01. A similar motif was previously described for the D(d) mouse MHC allele, but for none of the human HLA molecules for which a motif is known. Further investigation showed that one additional macaque allele, present in Indian rhesus macaques, Mamu-B*052:01, shares this same motif. These "G2" alleles were associated with the presence of specific residues in their B pocket. This pocket structure was found in 6% of macaque sequences but none of 950 human HLA class I alleles. Evolutionary studies using the "G2" alleles points to common ancestry for the macaque sequences, while convergent evolution is suggested when murine and macaque sequences are considered. This is the first detailed characterization of the pocket residues yielding this specific motif in nonhuman primates and mice, revealing a new supertype motif not present in humans.


Assuntos
Evolução Molecular , Antígenos de Histocompatibilidade/química , Macaca mulatta/imunologia , Camundongos/imunologia , Motivos de Aminoácidos , Animais , Linhagem Celular , Antígenos H-2/química , Antígeno de Histocompatibilidade H-2D , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Alinhamento de Sequência
19.
J Behav Med ; 27(4): 393-412, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15559735

RESUMO

The research evaluated an intervention strategy designed to prevent skin cancer in young adolescents. The intervention used parents as change agents to effectively communicate the risks of skin cancer and encourage their children to avoid high-risk sun-related behaviors while increasing positive sun-safe behaviors. Three hundred and forty parents in two regions of the United States were educated about the dangers of risky sun behaviors and how to convey information about skin cancer prevention to their children. Parents were then encouraged to talk with their children about these issues over a 1-month period prior to the onset of summer. Following this time period, children whose parents received and implemented the intervention materials were compared with a control sample of 129 children. These two groups were matched on age, gender, and school on number of sunburns and sunburn severity, attitudes and beliefs, and sunbathing behavior. Children in the treatment condition differed significantly from controls in the predicted directions on all outcome variables. The findings are discussed in terms of reducing skin cancer risk behaviors of children via parent-based intervention approaches.


Assuntos
Educação em Saúde , Pais/psicologia , Neoplasias Cutâneas/prevenção & controle , Adolescente , Criança , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Helioterapia/efeitos adversos , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Pais/educação , Fatores de Risco , Neoplasias Cutâneas/psicologia , Queimadura Solar/complicações , Queimadura Solar/prevenção & controle
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