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1.
PLoS One ; 19(5): e0299235, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38805414

RESUMO

In this study, we characterize the exopolymer produced by Halomonas sp. strain TGOS-10 -one of the organisms found enriched in sea surface oil slicks during the Deepwater Horizon oil spill. The polymer was produced during the early stationary phase of growth in Zobell's 2216 marine medium amended with glucose. Chemical and proton NMR analysis showed it to be a relatively monodisperse, high-molecular-mass (6,440,000 g/mol) glycoprotein composed largely of protein (46.6% of total dry weight of polymer). The monosaccharide composition of the polymer is typical to that of other marine bacterial exopolymers which are generally rich in hexoses, with the notable exception that it contained mannose (commonly found in yeast) as a major monosaccharide. The polymer was found to act as an oil dispersant based on its ability to effectively emulsify pure and complex oils into stable oil emulsions-a function we suspect to be conferred by the high protein content and high ratio of total hydrophobic nonpolar to polar amino acids (52.7:11.2) of the polymer. The polymer's chemical composition, which is akin to that of other marine exopolymers also having a high protein-to-carbohydrate (P/C) content, and which have been shown to effect the rapid and non-ionic aggregation of marine gels, appears indicative of effecting marine oil snow (MOS) formation. We previously reported the strain capable of utilising aromatic hydrocarbons when supplied as single carbon sources. However, here we did not detect biodegradation of these chemicals within a complex (surrogate Macondo) oil, suggesting that the observed enrichment of this organism during the Deepwater Horizon spill may be explained by factors related to substrate availability and competition within the complex and dynamic microbial communities that were continuously evolving during that spill.


Assuntos
Halomonas , Poluição por Petróleo , Halomonas/metabolismo , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/metabolismo , Petróleo/metabolismo , Água do Mar/microbiologia , Água do Mar/química , Tensoativos/metabolismo , Tensoativos/química , Biodegradação Ambiental
2.
J Med Syst ; 48(1): 55, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780820

RESUMO

Designing implants for large and complex cranial defects is a challenging task, even for professional designers. Current efforts on automating the design process focused mainly on convolutional neural networks (CNN), which have produced state-of-the-art results on reconstructing synthetic defects. However, existing CNN-based methods have been difficult to translate to clinical practice in cranioplasty, as their performance on large and complex cranial defects remains unsatisfactory. In this paper, we present a statistical shape model (SSM) built directly on the segmentation masks of the skulls represented as binary voxel occupancy grids and evaluate it on several cranial implant design datasets. Results show that, while CNN-based approaches outperform the SSM on synthetic defects, they are inferior to SSM when it comes to large, complex and real-world defects. Experienced neurosurgeons evaluate the implants generated by the SSM to be feasible for clinical use after minor manual corrections. Datasets and the SSM model are publicly available at https://github.com/Jianningli/ssm .


Assuntos
Redes Neurais de Computação , Crânio , Humanos , Crânio/cirurgia , Crânio/anatomia & histologia , Crânio/diagnóstico por imagem , Modelos Estatísticos , Processamento de Imagem Assistida por Computador/métodos , Procedimentos de Cirurgia Plástica/métodos , Próteses e Implantes
3.
Br J Radiol ; 97(1155): 574-582, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38276882

RESUMO

OBJECTIVES: To determine if multiparametric MRI prostate cancer (PC) lesion dimensions in different axes could distinguish between PC, grade group (GG) >2, and GG >3 on targeted transperineal biopsy and create and validate a predictive model on a separate cohort. METHODS: The maximum transverse, anterio-posterior, and cranio-caudal lesion dimensions were assessed against the presence of any cancer, GG >2, and GG >3 on biopsy by binary logistic regression. The optimum multivariate models were evaluated on a separate cohort. RESULTS: One hundred and ninety-three lesions from 148 patients were evaluated. Increased lesion volume, Prostate Specific Antigen (PSA), Prostate Imaging Reporting and Data System score, and decreased Apparent Diffusion Coefficient (ADC) were associated with increased GG (P < .001). The ratio of cranio-caudal to anterior-posterior lesion dimension increased from 1.20 (95% CI, 1.14-1.25) for GG ≤ 3 to 1.43 (95% CI, 1.28-1.57) for GG > 3 (P = .0022). The cranio-caudal dimension of the lesion was the strongest predictor of GG >3 (P = .000, area under the receiver operator characteristic curve [AUC] = 0.81). The best multivariate models had an AUC of 0.84 for cancer, 0.88 for GG > 2, and 0.89 for GG > 3. These models were evaluated on a separate cohort of 40 patients with 61 lesions. They demonstrated an AUC, sensitivity, and specificity of 0.82, 82.3%, and 55.5%, respectively, for the detection of cancer. For GG > 2, the models achieved an AUC of 0.84, sensitivity of 91.7%, and specificity of 69.4%. Additionally, for GG > 3, the models showed an AUC of 0.92, sensitivity of 88.9%, and specificity of 98.1%. CONCLUSIONS: Cranio-caudal lesion dimension when used in conjunction with other parameters can create a model superior to the Prostate Imaging Reporting and Data Systems score in predicting cancer. ADVANCES IN KNOWLEDGE: Higher-grade PC has a propensity to grow in the cranio-caudal direction, and this could be factored into MRI-based predictive models of prostate biopsy grade.


Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Próstata/patologia , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/patologia , Antígeno Prostático Específico , Imagem de Difusão por Ressonância Magnética/métodos , Estudos Retrospectivos , Biópsia Guiada por Imagem/métodos
5.
Proc Natl Acad Sci U S A ; 120(31): e2211117120, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37487084

RESUMO

Potato (Solanum sp., family Solanaceae) is the most important noncereal food crop globally. It has over 100 wild relatives in the Solanum section Petota, which features species with both sexual and asexual reproduction and varying ploidy levels. A pangenome of Solanum section Petota composed of 296 accessions was constructed including diploids and polyploids compared via presence/absence variation (PAV). The Petota core (genes shared by at least 97% of the accessions) and shell genomes (shared by 3 to 97%) are enriched in basic molecular and cellular functions, while the cloud genome (genes present in less than 3% of the member accessions) showed enrichment in transposable elements (TEs). Comparison of PAV in domesticated vs. wild accessions was made, and a phylogenetic tree was constructed based on PAVs, grouping accessions into different clades, similar to previous phylogenies produced using DNA markers. A cladewise pangenome approach identified abiotic stress response among the core genes in clade 1+2 and clade 3, and flowering/tuberization among the core genes in clade 4. The TE content differed between the clades, with clade 1+2, which is composed of species from North and Central America with reproductive isolation from species in other clades, having much lower TE content compared to other clades. In contrast, accessions with in vitro propagation history were identified and found to have high levels of TEs. Results indicate a role for TEs in adaptation to new environments, both natural and artificial, for Solanum section Petota.


Assuntos
Solanum tuberosum , Solanum , Elementos de DNA Transponíveis , Filogenia , Ploidias
6.
Front Public Health ; 11: 1122769, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37361156

RESUMO

Introduction: Absence from school is more frequent for children with chronic health conditions (CHCs) than their peers and may be one reason why average academic attainment scores are lower among children with CHCs. Methods: We determined whether school absence explains the association between CHCs and academic attainment through a systematic review of systematic reviews of comparative studies involving children with or without CHCs and academic attainment. We extracted results from any studies that tested whether school absence mediated the association between CHCs and academic attainment. Results: We identified 27 systematic reviews which included 441 unique studies of 7, 549, 267 children from 47 jurisdictions. Reviews either covered CHCs generally or were condition-specific (e.g., chronic pain, depression, or asthma). Whereas reviews found an association between a range of CHCs (CHCs generally, cystic fibrosis, hemophilia A, end-stage renal disease (pre-transplant), end-stage kidney disease (pre-transplant), spina bifida, congenital heart disease, orofacial clefts, mental disorders, depression, and chronic pain) and academic attainment, and though it was widely hypothesized that absence was a mediator in these associations, only 7 of 441 studies tested this, and all findings show no evidence of absence mediation. Conclusion: CHCs are associated with lower academic attainment, but we found limited evidence of whether school absence mediates this association. Policies that focus solely on reducing school absence, without adequate additional support, are unlikely to benefit children with CHCs. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=285031, identifier: CRD42021285031.


Assuntos
Dor Crônica , Fenda Labial , Fissura Palatina , Falência Renal Crônica , Criança , Humanos , Revisões Sistemáticas como Assunto , Doença Crônica , Instituições Acadêmicas
7.
Can J Ophthalmol ; 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36966818

RESUMO

OBJECTIVE: This study aimed to evaluate the long-term graft survivability of locally prestripped versus imported prestripped Descemet membrane endothelial keratoplasty (DMEK) grafts in Edmonton. DESIGN: Prospective cohort study of patients who underwent DMEK surgery between January 1, 2020, and December 31, 2020. PARTICIPANTS: All patients receiving a DMEK transplant during the study period in Edmonton. METHODS: Two local technicians were trained to prestrip DMEK grafts in Edmonton. When available, local tissue was prestripped for DMEK surgery; otherwise, prestripped DMEK grafts were imported from an accredited American eye bank. Patient characteristics and DMEK graft characteristics and DMEK survivability were evaluated and compared between the 2 groups. RESULTS: Thirty-two locally prestripped DMEK grafts and 35 imported prestripped DMEK grafts were used during the study period. Donor cornea characteristics and patient characteristics were similar between the 2 groups. Best-corrected visual acuity improved up to 6 months postoperatively and was 0.2 logMAR in the locally prestripped DMEK group and 0.2 logMAR in the imported DMEK group (p = 0.56). Rebubble rates were 25% in the locally prestripped DMEK group and 19% in the imported DMEK group (p = 0.43). There was 1 primary graft failure in each group (p = 0.93). Endothelial cell density decreased by 37% in the locally prestripped DMEK group and by 33% in the imported DMEK group 2 years after transplantation. CONCLUSIONS: The long-term survivability of locally prepared DMEK grafts is comparable with that of DMEK grafts imported from American eye banks.

8.
Can J Ophthalmol ; 58(5): 413-416, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35594911

RESUMO

OBJECTIVE: This study aimed to show the cost-effective benefits of creating a sustainable local program where Descemet membrane endothelial keratoplasty (DMEK) grafts were prepared locally instead of imported from American eye banks. DESIGN: Retrospective observational study. METHODS: In 2018, 2 local technicians were trained to prestrip DMEK grafts in Edmonton up to 2 days before surgery when local donor tissue was available. When no local tissue was available, prestripped DMEK grafts were imported from U.S. eye banks. The total cost of locally prepared and imported DMEK grafts over 27 months was compared with the cost that otherwise would have been accrued if all DMEK grafts had been imported. RESULTS: Over 27 months, 82 DMEK grafts (55.3%) were prepared locally and 63 DMEK grafts (44.7%) were imported. The total cost of preparing 82 grafts locally was $9349.19. The total cost of importing 63 prestripped DMEK grafts was $282 431.52. The combined total cost of locally prepared and imported DMEK grafts was $291 780.71. The total cost that otherwise would have been incurred if every graft was imported was $632 108.64. This difference in costs was $340 327.93 over 27 months. CONCLUSIONS: Establishing a sustainable program to make high-quality DMEK grafts with local donor corneas is a cost-effective alternative to importing prestripped DMEK grafts in Edmonton.


Assuntos
Lâmina Limitante Posterior , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Humanos , Lâmina Limitante Posterior/cirurgia , Endotélio Corneano , Análise Custo-Benefício , Coleta de Tecidos e Órgãos , Doadores de Tecidos , Estudos Retrospectivos
10.
World Neurosurg ; 166: e44-e51, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35772703

RESUMO

BACKGROUND: Growing evidence indicates fractal analysis (FA) has potential as a computational tool to assess tumor microvasculature in glioblastoma (GBM). As fractal parameters of microvasculature have shown to be reliable quantitative biomarkers in brain tumors, there has been similar success in measuring the architecture of tumor tissue using FA in other tumor types. However, evaluating fractal parameters of tissue structure in relation to the microvasculature has not yet been implemented in GBM. We aimed to assess the utility of this methodology in quantifying structural characteristics of GBM cytoarchitecture and vascularity by correlating fractal parameters with gene expression. METHODS: Formalin-fixed paraffin-embedded specimens were retrospectively collected from 43 patients following resection of a newly diagnosed GBM; 4 normal brain specimens were obtained from epilepsy surgeries as controls. Tumor samples were processed using FA employing a software-based box-counting method algorithm and custom messenger RNA expression assays. Fractal parameters were then correlated with clinical features, outcomes, and a panel of 92 genes associated with vascularity and angiogenesis. RESULTS: Statistical analysis demonstrated that fractal-based indices were not adequate parameters for distinction of GBM cytoarchitecture compared with normal brain specimens. Correlation analysis of our gene expression findings suggested that hematoxylin and eosin-based FA may have adequate sensitivity to detect associations with vascular gene expression. CONCLUSIONS: The combination of neuropathological assessment and histology does not provide optimized data for FA in GBM. However, an association between FA and gene expression in GBM of genes pertaining to cytoarchitecture and angiogenesis warrants further investigation.


Assuntos
Glioblastoma , Biomarcadores , Amarelo de Eosina-(YS) , Formaldeído , Fractais , Glioblastoma/irrigação sanguínea , Glioblastoma/genética , Glioblastoma/cirurgia , Hematoxilina , Humanos , Neovascularização Patológica/patologia , RNA Mensageiro , Estudos Retrospectivos
12.
J Cosmet Dermatol ; 19(9): 2306-2312, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32445602

RESUMO

BACKGROUND: The periocular and temporal regions are important aspects of beauty. The presence of reticular veins in these areas is undesirable and can also interfere with injection of neurotoxins to treat squint lines. 1064-nm Nd:YAG laser shows promise as an effective treatment modality with long-lasting effects. AIM: The aim of the study is to show that the long-pulsed, contact-cooled, variable spot-sized 1064-nm Nd:YAG laser is effective and safe, with good patient satisfaction and tolerability, and is able to achieve long-term results. METHODS: A retrospective study of 35 consecutive patients seen over a 3-year period in a private cosmetic clinic affiliated to the University of Toronto for periocular and temporal reticular veins was conducted. They were all treated with 1064-nm Nd:YAG laser. RESULTS: A total of 35 patients with an average age of 45.8 years old received treatment. 13 had lower eyelids treated, 9 had temples treated, 12 had both lower eyelids and temples treated, and 1 had both upper and lower eyelids treated. The first case of upper eyelid vein being treated with the 1064-nm Nd:YAG laser with great success after only 1 treatment is reported. 80% of the patients required only 1-2 treatment sessions. The average satisfaction score was 7.9 out of 10. The average pain score was 5.0 out of 10. 91% perceived the treatment outcome as excellent or good with the longest result lasting 33 months. There were 4 complications: 1 scabbing, 1 small burn, 1 skin darkening, and 1 teary eye. CONCLUSION: The study showed that the use of the long-pulsed, contact-cooled, variable spot-sized 1064-nm Nd:YAG laser is effective and safe, with good patient satisfaction and tolerability, and is able to achieve long-term results.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Terapia com Luz de Baixa Intensidade , Humanos , Lasers de Estado Sólido/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Veias
13.
Sci Data ; 7(1): 88, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32161269

RESUMO

Genome assembly of polyploid plant genomes is a laborious task as they contain more than two copies of the genome, are often highly heterozygous with a high level of repetitive DNA. Next Generation genome sequencing data representing one Chilean and five Peruvian polyploid potato (Solanum spp.) landrace genomes was used to construct genome assemblies comprising five taxa. Third Generation sequencing data (Linked and Long-read data) was used to improve the assembly for one of the genomes. Native landraces are valuable genetic resources for traits such as disease and pest resistance, environmental tolerance and other qualities of interest such as nutrition and fiber for breeding programs. The need for conservation and enhanced understanding of genetic diversity of cultivated potato from South America is also crucial to North American and European cultivars. Here, we report draft genomes from six polyploid potato landraces representing five taxa, illustrating how Third Generation Sequencing can aid in assembling polyploid genomes.


Assuntos
Genoma de Planta , Solanum tuberosum/genética , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Poliploidia , América do Sul
14.
Neurosurg Focus ; 48(2): E13, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32006951

RESUMO

OBJECTIVE: By looking at how the accuracy of preoperative brain mapping methods vary according to differences in the distance from the activation clusters used for the analysis, the present study aimed to elucidate how preoperative functional neuroimaging may be used in such a way that maximizes the mapping accuracy. METHODS: The eloquent function of 19 patients with a brain tumor or cavernoma was mapped prior to resection with both functional MRI (fMRI) and magnetoencephalography (MEG). The mapping results were then validated using direct cortical stimulation mapping performed immediately after craniotomy and prior to resection. The subset of patients with equivalent MEG and fMRI tasks performed for motor (n = 14) and language (n = 12) were evaluated as both individual and combined predictions. Furthermore, the distance resulting in the maximum accuracy, as evaluated by the J statistic, was determined by plotting the sensitivities and specificities against a linearly increasing distance threshold. RESULTS: fMRI showed a maximum mapping accuracy at 5 mm for both motor and language mapping. MEG showed a maximum mapping accuracy at 40 mm for motor and 15 mm for language mapping. At the standard 10-mm distance used in the literature, MEG showed a greater specificity than fMRI for both motor and language mapping but a lower sensitivity for motor mapping. Combining MEG and fMRI showed a maximum accuracy at 15 mm and 5 mm-MEG and fMRI distances, respectively-for motor mapping and at a 10-mm distance for both MEG and fMRI for language mapping. For motor mapping, combining MEG and fMRI at the optimal distances resulted in a greater accuracy than the maximum accuracy of the individual predictions. CONCLUSIONS: This study demonstrates that the accuracy of language and motor mapping for both fMRI and MEG is heavily dependent on the distance threshold used in the analysis. Furthermore, combining MEG and fMRI showed the potential for increased motor mapping accuracy compared to when using the modalities separately.Clinical trial registration no.: NCT01535430 (clinicaltrials.gov).


Assuntos
Mapeamento Encefálico/normas , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/fisiopatologia , Monitorização Neurofisiológica Intraoperatória/normas , Imageamento por Ressonância Magnética/normas , Magnetoencefalografia/normas , Mapeamento Encefálico/métodos , Neoplasias Encefálicas/cirurgia , Humanos , Monitorização Neurofisiológica Intraoperatória/métodos , Idioma , Imageamento por Ressonância Magnética/métodos , Magnetoencefalografia/métodos , Córtex Motor/diagnóstico por imagem , Córtex Motor/fisiopatologia , Córtex Motor/cirurgia
15.
Front Plant Sci ; 9: 1660, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30519250

RESUMO

Polyploidy or duplication of an entire genome occurs in the majority of angiosperms. The understanding of polyploid genomes is important for the improvement of those crops, which humans rely on for sustenance and basic nutrition. As climate change continues to pose a potential threat to agricultural production, there will increasingly be a demand for plant cultivars that can resist biotic and abiotic stresses and also provide needed and improved nutrition. In the past decade, Next Generation Sequencing (NGS) has fundamentally changed the genomics landscape by providing tools for the exploration of polyploid genomes. Here, we review the challenges of the assembly of polyploid plant genomes, and also present recent advances in genomic resources and functional tools in molecular genetics and breeding. As genomes of diploid and less heterozygous progenitor species are increasingly available, we discuss the lack of complexity of these currently available reference genomes as they relate to polyploid crops. Finally, we review recent approaches of haplotyping by phasing and the impact of third generation technologies on polyploid plant genome assembly.

16.
Histopathology ; 73(3): 369-385, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29573451

RESUMO

Optimal patient management benefits from comprehensive and accurate pathology reports that contribute to cancer staging and prognostication. Proforma reports are used in many countries, but these vary in their structure and implementation. The International Collaboration on Cancer Reporting (ICCR) is an alliance formed by the Royal College of Pathologists of Australasia, the Royal College of Pathologists of the United Kingdom, the College of American Pathologists, the Canadian Partnership Against Cancer the European Society of Pathology and the American Society of Clinical Pathology (ASCP), with the aim of developing an evidence-based reporting data set for each cancer site. It is argued that this should reduce the global burden of cancer data set development and reduplication of effort by different international institutions that commission, publish and maintain standardised cancer reporting data sets. The resultant standardisation of cancer reporting will benefit not only those countries directly involved in the collaboration but also others not in a position to develop their own data sets. We describe the development of a cancer data set by the ICCR expert panel for the reporting of the main malignant liver tumours: intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma and hepatocellular carcinoma and present the 'required' and 'recommended' elements to be included in the report with an explanatory commentary. This data set incorporates definitions and classifications in the most recent World Health Organisation (WHO) publication on hepatic malignancies (4th edition) and the recently published tumour-node-metastasis (TNM)8 staging system. Widespread adoption and implementation of this data set will enable consistent and accurate data collection, comparison of epidemiological and pathological parameters between different populations, facilitate research and ultimately result in better patient outcomes.


Assuntos
Conjuntos de Dados como Assunto , Oncologia/normas , Patologia Clínica/normas , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/patologia , Humanos , Tumor de Klatskin/patologia , Neoplasias Hepáticas/patologia , Projetos de Pesquisa/normas
17.
J Med Chem ; 60(16): 7029-7042, 2017 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-28682065

RESUMO

A series of acidic diaryl ether heterocyclic sulfonamides that are potent and subtype selective NaV1.7 inhibitors is described. Optimization of early lead matter focused on removal of structural alerts, improving metabolic stability and reducing cytochrome P450 inhibition driven drug-drug interaction concerns to deliver the desired balance of preclinical in vitro properties. Concerns over nonmetabolic routes of clearance, variable clearance in preclinical species, and subsequent low confidence human pharmacokinetic predictions led to the decision to conduct a human microdose study to determine clinical pharmacokinetics. The design strategies and results from preclinical PK and clinical human microdose PK data are described leading to the discovery of the first subtype selective NaV1.7 inhibitor clinical candidate PF-05089771 (34) which binds to a site in the voltage sensing domain.


Assuntos
Canal de Sódio Disparado por Voltagem NAV1.7/metabolismo , Éteres Fenílicos/farmacologia , Sulfonamidas/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Linhagem Celular , Citocromo P-450 CYP2C9/metabolismo , Inibidores do Citocromo P-450 CYP2C9/síntese química , Inibidores do Citocromo P-450 CYP2C9/química , Inibidores do Citocromo P-450 CYP2C9/farmacocinética , Inibidores do Citocromo P-450 CYP2C9/farmacologia , Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A/síntese química , Inibidores do Citocromo P-450 CYP3A/química , Inibidores do Citocromo P-450 CYP3A/farmacocinética , Inibidores do Citocromo P-450 CYP3A/farmacologia , Desenho de Fármacos , Humanos , Microssomos Hepáticos/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.7/química , Éteres Fenílicos/síntese química , Éteres Fenílicos/química , Éteres Fenílicos/farmacocinética , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química , Sulfonamidas/farmacocinética , Bloqueadores do Canal de Sódio Disparado por Voltagem/síntese química , Bloqueadores do Canal de Sódio Disparado por Voltagem/química , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacocinética
18.
Metabolomics ; 12: 112, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27398079

RESUMO

INTRODUCTION: An exceptionally interesting stress response of Pseudomonas putida strains to toxic substances is the induction of efflux pumps that remove toxic chemical substances from the bacterial cell out to the external environment. To exploit these microorganisms to their full potential a deeper understanding of the interactions between the bacteria and organic solvents is required. Thus, this study focuses on investigation of metabolic changes in P. putida upon exposure to toluene. OBJECTIVE: Investigate observable metabolic alterations during interactions of three strains of P. putida (DOT-T1E, and its mutants DOT-T1E-PS28 and DOT-T1E-18) with the aromatic hydrocarbon toluene. METHODS: The growth profiles were measured by taking optical density (OD) measurement at 660 nm (OD660) at various time points during incubation. For fingerprinting analysis, Fourier-transform infrared (FT-IR) spectroscopy was used to investigate any phenotypic changes resulting from exposure to toluene. Metabolic profiling analysis was performed using gas chromatography-mass spectrometry (GC-MS). Principal component-discriminant function analysis (PC-DFA) was applied to the FT-IR data while multiblock principal component analysis (MB-PCA) and N-way analysis of variance (N-way ANOVA) were applied to the GC-MS data. RESULTS: The growth profiles demonstrated the effect of toluene on bacterial cultures and the results suggest that the mutant P. putida DOT-T1E-18 was more sensitive (significantly affected) to toluene compared to the other two strains. PC-DFA on FT-IR data demonstrated the differentiation between different conditions of toluene on bacterial cells, which indicated phenotypic changes associated with the presence of the solvent within the cell. Fifteen metabolites associated with this phenotypic change, in P. putida due to exposure to solvent, were from central metabolic pathways. Investigation of MB-PCA loading plots and N-way ANOVA for condition | strain × time blocking (dosage of toluene) suggested ornithine as the most significant compound that increased upon solvent exposure. CONCLUSION: The combination of metabolic fingerprinting and profiling with suitable multivariate analysis revealed some interesting leads for understanding the mechanism of Pseudomonas strains response to organic solvent exposure.

19.
Plast Reconstr Surg ; 137(4): 1125-1140, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27018668

RESUMO

BACKGROUND: Three formulations of botulinum toxin are available for facial rhytides. It is unclear which formulation offers the greatest balance of benefits and harms. The objective of this study was to conduct a systematic review with meta-analyses to compare formulations of botulinum toxin for reduction of facial rhytides at the glabella. METHODS: The authors' protocol was registered with the International Prospective Register of Systematic Reviews (CRD4201200377). A systematic literature search was performed identifying double-blind studies. The authors assessed 1-, 3-, and 4-month follow-up. The authors performed pairwise meta-analyses using random effects models to compare response rates among the three botulinum formulations and a network meta-analysis. RESULTS: A total of 18 studies (3082 patients) were included. At 30-, 90-, and 120-day follow-up, all medications with available data showed statistically significantly increased treatment response versus placebo. Only high-dose onabotulinum toxin (compared to standard-dose onabotulinum toxin) offered additional benefit at 30 days. Exploratory analysis using network meta-analysis mostly suggested insufficient evidence of incremental benefits when comparing specific formulations. CONCLUSIONS: Evidence supporting benefits versus placebo of the different formulations was clear over time. Comparisons between active formulations were rare and typically based on single trials of small to moderate sample size. The data suggest some gains with high-dose onabotulinum toxin (relative to standard dose), whereas exploratory indirect comparisons between active formulations were largely associated with inconclusive findings. Future studies should undertake head-to-head comparisons of the different formulations and ensure longer follow-up to best inform the accumulating evidence base. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Técnicas Cosméticas , Fármacos Neuromusculares/administração & dosagem , Envelhecimento da Pele , Humanos , Modelos Estatísticos , Avaliação de Resultados em Cuidados de Saúde
20.
Nephrourol Mon ; 8(1): e29967, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26981495

RESUMO

BACKGROUND: Post-operative single dose intravesical chemotherapy (PSDIVC) in patients with non-muscle invasive bladder cancer has been shown to reduce recurrence rates by up to 39%. However, some studies have suggested poor compliance with PSDIVC stating logistical issues and reluctance to give chemotherapy prior to histological confirmation as some of the reasons. OBJECTIVES: This study aims to analyse appropriate administration of PSDIVC practice in St. Mary's Hospital against European Association of Urology guidelines and implement an intervention bundle to improve practice. PATIENTS AND METHODS: All patients that underwent transurethral resection of bladder tumour (TURBT) between March 2012 and February 2013 were analysed retrospectively to review indication for post-operative chemotherapy, instillation rates and limiting factors preventing appropriate instillation. An intervention bundle including pre-operative delivery of mitomycin C (MMC) to the theatre suite, proforma placed in the operative notes and designated roles for PSDIVC induction was introduced to improve instillation and documentation rates. Prospective re-audit data was collected over six months between July 2013 and December 2013 following intervention. RESULTS: Sixty-four patients in group A underwent TURBT prior to introduction of the intervention bundle. Fifty-four patients had non-muscle invasive bladder cancer (NMIBC), which would have been eligible for PSDIVC. Fifteen (28% of NMIBC) were administered PSDIVC. Twenty-three (36% of all patients) were either given PSDIVC or had a documented contraindication. Thirty-one patients in group B underwent TURBT following induction of intervention bundle. Twelve (50% of NMIBC) patients were given PSDIVC. Twenty-eight (90% of all patients) were either given PSDIVC or had a documented contraindication. CONCLUSIONS: The intervention bundle prompted increased administration of PSDIVC and documentation. Similar centres may benefit from an intervention to improve compliance.

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