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1.
Nat Commun ; 15(1): 3679, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693149

RESUMO

HPV vaccination with concomitant HPV-based screening of young women has been proposed for faster cervical cancer elimination. We describe the baseline results of a population-based trial of this strategy to reduce the incidence of HPV. All 89,547 women born 1994-1999 and resident in the capital region of Sweden were personally invited to concomitant HPV vaccination and HPV screening with 26,125 women (29.2%) enrolled between 2021-05-03 and 2022-12-31. Baseline HPV genotyping of cervical samples from the study participants finds, compared to pre-vaccination prevalences, a strong decline of HPV16 and 18 in birth cohorts previously offered vaccination, some decline for cross-protected HPV types but no decline for HPV types not targeted by vaccines. Our dynamic transmission modelling predicts that the trial could reduce the incidence of high-risk HPV infections among the 1994-1998 cohorts by 62-64% in 3 years. Baseline results are prevalences of HPV infection, validated transmission model projections, and power estimates for evaluating HPV incidence reductions at follow-up (+/-0.1% with 99.9% confidence). In conclusion, concomitant HPV vaccination and HPV screening appears to be a realistic option for faster cervical cancer elimination. Clinicaltrials.gov identifier: NCT04910802; EudraCT number: 2020-001169-34.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/epidemiologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/imunologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/uso terapêutico , Adulto , Suécia/epidemiologia , Adulto Jovem , Vacinação , Adolescente , Incidência , Programas de Rastreamento , Prevalência , Pessoa de Meia-Idade , Detecção Precoce de Câncer , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/imunologia , Papillomavirus Humano
2.
J Med Virol ; 95(12): e29332, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38115556

RESUMO

The International Human Papillomavirus (HPV) Reference Center (IHRC) confirms and assigns type numbers to novel HPV types, maintains a reference clone repository, and issues international proficiency panels for HPV screening and genotyping. Furthermore, the Center coordinates the Global HPV Reference Laboratory Network that promotes collaboration and international exchange of experiences among national HPV reference laboratories, to further international standardization and quality assurance in the HPV field. The established HPV types (n = 225) belong to 5 different genera: alpha (n = 65), beta (n = 54), gamma (n = 102), mu (n = 3) and nu (n = 1). Since the last published IHRC overview in 2018, 6 novel types have been established, with 5/6 belonging to the gamma genus and 1/6 to beta genus. Also, 474 reference clones have been provided to 55 different research laboratories and the global proficiency program for HPV genotyping has seen an increasing proficiency (despite a decrease seen in 2019), from 68% proficiency in 2017 to 77.3% in 2022. The first proficiency study for HPV screening found an international proficiency of up to 77%. In summary, increasing complexity of the HPVs and demands on quality assurance in the era of cervical cancer elimination requires international efforts to support proficiency and recognized quality and order among HPV types.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Papillomavirus Humano , Infecções por Papillomavirus/diagnóstico , Papillomaviridae/genética , Padrões de Referência , Programas de Rastreamento , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle
3.
Energy Fuels ; 36(21): 13084-13093, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36366752

RESUMO

Biofuels are required to reach the target set out by the European Commission's Transport mandate in the RED II (Renewable Energy Directive) for 2020-2030. To avoid indirect land use change, waste biomass resources such as sunflower husks can be used for advanced biofuel production. A process simulation and technoeconomic assessment of three fast pyrolysis plant scenarios were conducted. The nature of the waste feedstock has an effect on the value chain configuration, fast pyrolysis, and upgrading process design. Considering the difficulties with the transport and storage of biogenic waste due to low bulk density or hazardous and pathogenic content in case of transporting untreated sunflower husks, it is recommended to use a hub-and-spoke type of decentralized value chain configuration. The fast pyrolysis plants are located close to the feedstock, and the fast pyrolysis bio-oil (FPBO) is transported to a single upgrading facility, colocated at an existing refinery. The upgraded FPBO is then cofed into an FCC (fluidized catalyst cracker), where partially green biofuels such as gasoline and diesel are produced. For the fast pyrolysis process design, Scenario 2, treating 10 t/h of dry biomass with electricity and steam as coproducts, has the most favorable economic results with a total capital investment (TCI) of 78 million Euro and operating expenses (OPEX) of 6 million Euro.

4.
Eur J Cancer ; 172: 107-118, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35763870

RESUMO

BACKGROUND: The multi-receptor tyrosine kinase inhibitor pazopanib is approved for the treatment of advanced soft-tissue sarcoma and has also shown activity in other sarcoma subtypes. However, its clinical efficacy is highly variable, and no reliable predictors exist to select patients who are likely to benefit from this drug. PATIENTS AND METHODS: We analysed the molecular profiles and clinical outcomes of patients with pazopanib-treated sarcoma enrolled in a prospective observational study by the German Cancer Consortium, DKTK MASTER, that employs whole-genome/exome sequencing and transcriptome sequencing to inform the care of young adults with advanced cancer across histology and patients with rare cancers. RESULTS: Among 109 patients with available whole-genome/exome sequencing data, there was no correlation between clinical parameters, specific genetic alterations or mutational signatures and clinical outcome. In contrast, the analysis of a subcohort of 62 patients who underwent molecular analysis before pazopanib treatment and had transcriptome sequencing data available showed that mRNA levels of NTRK3 (hazard ratio [HR] = 0.53, p = 0.021), IGF1R (HR = 1.82, p = 0.027) and KDR (HR = 0.50, p = 0.011) were independently associated with progression-free survival (PFS). Based on the expression of these receptor tyrosine kinase genes, i.e. the features NTRK3-high, IGF1R-low and KDR-high, we developed a pazopanib efficacy predictor that stratified patients into three groups with significantly different PFS (p < 0.0001). Application of the pazopanib efficacy predictor to an independent cohort of patients with pazopanib-treated sarcoma from DKTK MASTER (n = 43) confirmed its potential to separate patient groups with significantly different PFS (p = 0.02), whereas no such association was observed in patients with sarcoma from DKTK MASTER (n = 97) or The Cancer Genome Atlas sarcoma cohort (n = 256) who were not treated with pazopanib. CONCLUSION: A score based on the combined expression of NTRK3, IGF1R and KDR allows the identification of patients with sarcoma and with good, intermediate and poor outcome following pazopanib therapy and warrants prospective investigation as a predictive tool to optimise the use of this drug in the clinic.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Expressão Gênica , Humanos , Indazóis/uso terapêutico , Estudos Prospectivos , Pirimidinas , Sarcoma/tratamento farmacológico , Sarcoma/genética , Neoplasias de Tecidos Moles/tratamento farmacológico , Sulfonamidas , Adulto Jovem
6.
Haematologica ; 107(8): 1891-1901, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35045690

RESUMO

The outcomes of patients with multiple myeloma (MM) refractory to immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs) remain poor. In this study, we performed whole genome and transcriptome sequencing of 39 heavily pretreated relapsed/refractory MM (RRMM) patients to identify mechanisms of resistance and potential therapeutic targets. We observed a high mutational load and indications of increased genomic instability. Recurrently mutated genes in RRMM, which had not been previously reported or only observed at a lower frequency in newly diagnosed MM, included NRAS, BRAF, TP53, SLC4A7, MLLT4, EWSR1, HCFC2, and COPS3. We found multiple genomic regions with bi-allelic events affecting tumor suppressor genes and demonstrated a significant adverse impact of bi-allelic TP53 alterations on survival. With regard to potentially resistance conferring mutations, recurrently mutated gene networks included genes with relevance for PI and IMiD activity; the latter particularly affecting members of the Cereblon and the COP9 signalosome complex. We observed a major impact of signatures associated with exposure to melphalan or impaired DNA double-strand break homologous recombination repair in RRMM. The latter coincided with mutations in genes associated with PARP inhibitor sensitivity in 49% of RRMM patients; a finding with potential therapeutic implications. In conclusion, this comprehensive genomic characterization revealed a complex mutational and structural landscape in RRMM and highlights potential implications for therapeutic strategies.


Assuntos
Mieloma Múltiplo , Resistencia a Medicamentos Antineoplásicos/genética , Genômica , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mutação , Inibidores de Proteassoma/uso terapêutico
7.
Environ Sci Pollut Res Int ; 28(47): 66575-66588, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34235695

RESUMO

This paper investigates the impact of several comprehensive risks such as credit risk, capital risk, liquidity risk, and insolvency risks on Pakistani banks' technical efficiency to assess the nexus between environmental investments with technical efficiency of banks. It also probes into the effect of competition among the Pakistani banks on technical efficiency. The data envelopment analysis (DEA) CCR and BCC models are used to estimate technical, purely technical, and scale efficiencies of the Pakistani banks. The Lerner index measures the banking competition. For estimation, the bootstrap truncated regression is used as an econometric technique. The robustness of results is cross-checked by using an alternative econometric technique (fractional logit regression) and an alternative competition measure (Boone indicator). The study revealed that capital risk has a positive impact on scale efficiency and insolvency risk has a negative impact on technical and pure technical efficiencies. Similarly, there is a positive significant relationship between technical efficiency and environmental investment. Furthermore, the competition has a significant negative effect on Pakistani banks' technical and pure technical efficiencies. The results suggest that the efficiency of the Pakistani banks is significantly affected by bank size, taxation, diversification, operational cost management, banking development, trade openness, and infrastructure development, which ultimately promotes environmental efficiency and protection. The comparative study indicates that the state-owned banks have higher technical, pure technical, and scale efficiencies than the private, foreign, and Islamic banks.


Assuntos
Eficiência , Investimentos em Saúde
8.
Cent European J Urol ; 74(1): 71-75, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33976919

RESUMO

INTRODUCTION: Kidney stone disease is a common disease with high recurrence rates. Sufficient intake of water is the cornerstone in primary prevention of stone disease. However, the mineral composition of water can affect urinary minerals and influence stone formation. The aim of this study is to assess the variation in the mineral composition of bottled sparkling or carbonated drinking water across Europe. MATERIAL AND METHODS: The two largest supermarket chains in each participating country were visited to obtain data on mineral composition regarding bicarbonate, calcium, magnesium, potassium, sodium and sulphates of sparkling or carbonated waters by reading the ingredient labels on the bottles supplied by the manufacturers. Alternatively, the web-shops of these supermarkets were consulted. RESULTS: In total, 126 sparkling water brands across ten European countries were analysed regarding mineral composition. The median concentrations per mineral varied greatly. The greatest variation in median mineral content was found for sodium and sulphates with levels ranging from 3.1 mg/l to 63.0 mg/l and 6.0 mg/l to 263.0 mg/l respectively. A wide distribution of calcium content was found in Switzerland, with calcium levels reaching up to 581.6 mg/l. CONCLUSIONS: This study confirms that the mineral composition of sparkling or carbonated water varies greatly across Europe. Patients with kidney stone disease should be aware that the mineral content of water may influence stone formation and be mindful of the great variation that exists between different water brands. Mineral water can be a source of potential promotors or inhibitors of stone formation and patients and urologists need to be mindful of this.

9.
J Transl Med ; 19(1): 204, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980253

RESUMO

BACKGROUND: Soft-tissue sarcomas (STS) are a heterogeneous group of mesenchymal tumors for which response to immunotherapies is not well established. Therefore, it is important to risk-stratify and identify STS patients who will most likely benefit from these treatments. RESULTS: To reveal shared and distinct methylation signatures present in STS, we performed unsupervised deconvolution of DNA methylation data from the TCGA sarcoma and an independent validation cohort. We showed that leiomyosarcoma can be subclassified into three distinct methylation groups. More importantly, we identified a component associated with tumor-infiltrating leukocytes, which suggests varying degrees of immune cell infiltration in STS subtypes and an association with prognosis. We further investigated the genomic alterations that may influence tumor infiltration by leukocytes including RB1 loss in undifferentiated pleomorphic sarcomas and ELK3 amplification in dedifferentiated liposarcomas. CONCLUSIONS: In summary, we have leveraged unsupervised methylation-based deconvolution to characterize the immune compartment and molecularly stratify subtypes in STS, which may benefit precision medicine in the future.


Assuntos
Leiomiossarcoma , Sarcoma , Neoplasias de Tecidos Moles , Epigenoma , Genômica , Humanos , Leiomiossarcoma/genética , Proteínas Proto-Oncogênicas c-ets , Sarcoma/genética
10.
J Endourol ; 35(2): 206-214, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32762257

RESUMO

Introduction: Kidney stone disease (KSD) is a highly prevalent disease worldwide. As water intake and its mineral content influence stone formation and recurrence, patients and physicians must be aware of the mineral content of drinkable water. We analyzed commercial bottled still water within Europe to assess the variation in its mineral composition across different manufacturers and countries. Materials and Methods: Data on the mineral composition of bottled still water regarding bicarbonate, calcium, magnesium, potassium, sodium, and sulfate concentration (mg/L) were collected from ten European countries. To collect the data, the two main supermarket chains in each participating country were either visited to check for the ingredient label on bottles or the online shop was consulted through the website of the supermarket in question. Descriptive statistics such as simple boxplots were used to illustrate the variation in mineral content. Results: One hundred eighty-two different commercial water brands were analyzed. Up to a fivefold variation in average concentrations per mineral between countries was observed. For calcium, a wide distribution was found in France and Switzerland compared with other countries with calcium levels ranging from 10.5 to 565 mg/L and 8.4 to 579 mg/L, respectively. By consuming 2 L of water with such high calcium levels, the daily reference intake for calcium is already achieved. Conclusions: The mineral content of bottled still water across Europe varies greatly. For patients with KSD it is important to be aware of the mineral content of the water they drink, as it might influence stone recurrence rates and necessitate alterations of their diet.


Assuntos
Água Potável , Águas Minerais , Água Potável/análise , Europa (Continente) , França , Humanos , Águas Minerais/análise , Minerais
11.
PLoS One ; 15(8): e0237558, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785285

RESUMO

BACKGROUND: The Covid-19 pandemic threatens to overwhelm scarce clinical resources. Risk factors for severe illness must be identified to make efficient resource allocations. OBJECTIVE: To evaluate risk factors for severe illness. DESIGN: Retrospective, observational case series. SETTING: Single-institution. PARTICIPANTS: First 117 consecutive patients hospitalized for Covid-19 from March 1 to April 12, 2020. EXPOSURE: None. MAIN OUTCOMES AND MEASURES: Intensive care unit admission or death. RESULTS: In-hospital mortality was 24.8% and average total length of stay was 11.82 days (95% CI: 10.01 to 13.63 days). 30.8% of patients required intensive care unit admission and 29.1% required mechanical ventilation. Multivariate regression identified the amount of supplemental oxygen required at admission (OR: 1.208, 95% CI: 1.011-1.443, p = .037), sputum production (OR: 6.734, 95% CI: 1.630-27.812, p = .008), insulin dependent diabetes mellitus (OR: 11.873, 95% CI: 2.218-63.555, p = .004) and chronic kidney disease (OR: 4.793, 95% CI: 1.528-15.037, p = .007) as significant risk factors for intensive care unit admission or death. Of the 48 patients who were admitted to the intensive care unit or died, this occurred within 3 days of arrival in 42%, within 6 days in 71%, and within 9 days in 88% of patients. CONCLUSIONS: At our regional medical center, patients with Covid-19 had an average length of stay just under 12 days, required ICU care in 31% of cases, and had a 25% mortality rate. Patients with increased sputum production and higher supplemental oxygen requirements at admission, and insulin dependent diabetes or chronic kidney disease may be at increased risk for severe illness. A model for predicting intensive care unit admission or death with excellent discrimination was created that may aid in treatment decisions and resource allocation. Early identification of patients at increased risk for severe illness may lead to improved outcomes in patients hospitalized with Covid-19.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Hospitalização , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Estado Terminal , Feminino , Alocação de Recursos para a Atenção à Saúde , Mortalidade Hospitalar , Hospitais Comunitários , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Maryland/epidemiologia , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Respiração Artificial , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , SARS-CoV-2
12.
Front Immunol ; 11: 120, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117271

RESUMO

The manifestation of brain metastases in patients with advanced melanoma is a common event that limits patient's survival and quality of life. The immunosuppressive properties of the brain parenchyma are very different compared to the rest of the body, making it plausible that the current success of cancer immunotherapies is specifically limited here. In melanoma brain metastases, the reciprocal interplay between immunosuppressive mediators such as indoleamine 2, 3-dioxygenase (IDO) or programmed cell death-ligand 1 (PD-L1) in the context of neoplastic transformation are far from being understood. Therefore, we analyzed the immunoreactive infiltrate (CD45, CD3, CD8, Forkhead box P3 [FoxP3], CD11c, CD23, CD123, CD68, Allograft Inflammatory factor 1[AIF-1]) and PD-L1 with respect to IDO expression and localization in melanoma brain metastases but also in matched metastases at extracranial sites to correlate intra- and interpatient data with therapy response and survival. Comparative tissue analysis identified macrophages/microglia as the major source of IDO expression in melanoma brain metastases. In contrast to the tumor infiltrating lymphocytes, melanoma cells per se exhibited low IDO expression levels paralleled by cell surface presentation of PD-L1 in intracranial metastases. Absolute numbers and pattern of IDO-expressing cells in metastases of the brain correlated with recruitment and localization of CD8+ T cells, implicating dynamic impact on the regulation of T cell function in the brain parenchyma. However, paired analysis of matched intra- and extracranial metastases identified significantly lower fractions of cytotoxic CD8+ T cells in intracranial metastases while all other immune cell populations remain unchanged. In line with the already established clinical benefit for PD-L1 expression in extracranial melanoma metastases, Kaplan-Meier analyses correlated PD-L1 expression in brain metastases with favorable outcome in advanced melanoma patients undergoing immune checkpoint therapy. In summary, our data provide new insights into the landscape of immunosuppressive factors in melanoma brain metastases that may be useful in the implication of novel therapeutic strategies for patients undergoing cancer immunotherapy.


Assuntos
Neoplasias Encefálicas/imunologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Macrófagos/metabolismo , Melanoma/imunologia , Microglia/metabolismo , Idoso , Encéfalo/imunologia , Encéfalo/metabolismo , Neoplasias Encefálicas/patologia , Linfócitos T CD8-Positivos/imunologia , Estudos de Coortes , Feminino , Humanos , Imunoterapia , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Microambiente Tumoral/imunologia
13.
BMC Bioinformatics ; 20(1): 272, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138115

RESUMO

BACKGROUND: Establishment of telomere maintenance mechanisms is a universal step in tumor development to achieve replicative immortality. These processes leave molecular footprints in cancer genomes in the form of altered telomere content and aberrations in telomere composition. To retrieve these telomere characteristics from high-throughput sequencing data the available computational approaches need to be extended and optimized to fully exploit the information provided by large scale cancer genome data sets. RESULTS: We here present TelomereHunter, a software for the detailed characterization of telomere maintenance mechanism footprints in the genome. The tool is implemented for the analysis of large cancer genome cohorts and provides a variety of diagnostic diagrams as well as machine-readable output for subsequent analysis. A novel key feature is the extraction of singleton telomere variant repeats, which improves the identification and subclassification of the alternative lengthening of telomeres phenotype. We find that whole genome sequencing-derived telomere content estimates strongly correlate with telomere qPCR measurements (r = 0.94). For the first time, we determine the correlation of in silico telomere content quantification from whole genome sequencing and whole genome bisulfite sequencing data derived from the same tumor sample (r = 0.78). An analogous comparison of whole exome sequencing data and whole genome sequencing data measured slightly lower correlation (r = 0.79). However, this is considerably improved by normalization with matched controls (r = 0.91). CONCLUSIONS: TelomereHunter provides new functionality for the analysis of the footprints of telomere maintenance mechanisms in cancer genomes. Besides whole genome sequencing, whole exome sequencing and whole genome bisulfite sequencing are suited for in silico telomere content quantification, especially if matched control samples are available. The software runs under a GPL license and is available at https://www.dkfz.de/en/applied-bioinformatics/telomerehunter/telomerehunter.html .


Assuntos
Simulação por Computador , Genoma , Neoplasias/genética , Software , Telômero/genética , Sequência de Bases , Glioblastoma/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Meduloblastoma/genética , Sequenciamento do Exoma , Sequenciamento Completo do Genoma
14.
Nanoscale ; 11(9): 3888-3895, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30758042

RESUMO

We have studied the epitaxy and structural characterization of monolithic n-GaN/Al/p-AlGaN nanowire heterostructures. It is found that high quality, nearly defect free, full shell epitaxial Al can be grown in situ on Al(Ga)N nanowires and vice versa. Detailed scanning transmission electron microscopy (STEM), high-resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD) suggest that the Al (111) plane maintains an epitaxial relationship with Al(Ga)N (0001) in the nanowire growth direction. Full ultraviolet composition range (340 nm-210 nm) Al/Al(Ga)N core-double shell nanowire backward diode characteristics were investigated. We have demonstrated a monolithic n++-GaN/Al/p++-Al(Ga)N nanowire backward diode, wherein an epitaxial Al layer serves as the tunnel junction. Such an Al(Ga)N-based n-p-n nanowire backward diode exhibits record low resistivity (<1.5 × 10-4Ω cm2) and a low turn-on voltage of ∼2.7 V.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 213: 192-198, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30685558

RESUMO

The potential of fluorescence spectroscopy is exploited for the characterization and comparison of different turmeric varieties based on curcuminoids content in turmeric powders. Fluorescence spectra from turmeric powders has been acquired by using excitation wavelengths from 300 to 470 nm with step of 10 nm to investigate the effect of excitation wavelengths on the emission of valuable ingredients for their characterization. Emission spectra revealed that fresh wet turmeric rhizomes show emission bands at 571 nm which is due to curcumin. It is found that main ingredient of turmeric powder is curcumin and best excitation wavelength is 467 nm for its maximum emission intensity. High Pressure Liquid Chromatography (HPLC) was used as alternate standard technique for determination of curcuminoid content in the reference samples. The curcumin content in the commercially available local turmeric brands were also evaluated, one brand showed significant covariance from standard fluorescent spectra of turmeric meaning this particular brand contained minimum curcumin content or have been severely adultered. In the next step the powders were heated at different temperatures from 60 °C to 150 °C (Normal cooking & frying temperatures) to observe the difference in emission spectra particularly keeping in view the molecular composition and curcuminoid content in turmeric. The results indicate that curcumin content gradually decreases above 90 °C. Principal component analysis (PCA) has been employed on all the data to statistically differentiate small molecular changes and adulteration by covariance calculations.


Assuntos
Curcuma/química , Curcumina/análise , Espectrometria de Fluorescência/métodos , Cromatografia Líquida de Alta Pressão , Dessecação , Padrões de Referência
16.
Nat Commun ; 9(1): 144, 2018 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-29321523

RESUMO

Leiomyosarcoma (LMS) is an aggressive mesenchymal malignancy with few therapeutic options. The mechanisms underlying LMS development, including clinically actionable genetic vulnerabilities, are largely unknown. Here we show, using whole-exome and transcriptome sequencing, that LMS tumors are characterized by substantial mutational heterogeneity, near-universal inactivation of TP53 and RB1, widespread DNA copy number alterations including chromothripsis, and frequent whole-genome duplication. Furthermore, we detect alternative telomere lengthening in 78% of cases and identify recurrent alterations in telomere maintenance genes such as ATRX, RBL2, and SP100, providing insight into the genetic basis of this mechanism. Finally, most tumors display hallmarks of "BRCAness", including alterations in homologous recombination DNA repair genes, multiple structural rearrangements, and enrichment of specific mutational signatures, and cultured LMS cells are sensitive towards olaparib and cisplatin. This comprehensive study of LMS genomics has uncovered key biological features that may inform future experimental research and enable the design of novel therapies.


Assuntos
Leiomiossarcoma/genética , Leiomiossarcoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromotripsia , Variações do Número de Cópias de DNA , Feminino , Duplicação Gênica , Perfilação da Expressão Gênica , Genes do Retinoblastoma , Genes p53 , Genômica , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Análise de Sequência de RNA , Homeostase do Telômero , Sequenciamento do Exoma , Adulto Jovem
17.
J Vasc Surg ; 67(3): 838-847, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29276109

RESUMO

OBJECTIVE: The objective of this study was to determine the natural progression of popliteal artery aneurysms (PAAs) and clinical variables associated with their accelerated growth. METHODS: Retrospective chart review of 224 patients with encounters between January 2008 and May 2016 and with at least one PAA was conducted. From this group, 65 asymptomatic patients had either unilateral (n = 43) or bilateral (n = 22) PAAs that were observed for at least 1 year of medical management before intervention. We divided these aneurysms into two groups based on whether their overall growth rate was above or below the eventual mean. Aneurysm diameter was taken from duplex ultrasound and computed tomography angiography. RESULTS: There were 87 aneurysms evaluated among 65 patients. Mean age at diagnosis was 70.9 years (standard deviation [SD], 9.39 years), and 64 patients were male (98%); 50 (77%) were white and 7 (11%) were African American. The average body mass index was 27.69 (SD, 4.90). At or before initial diagnosis, 61 (94%) patients had a concomitant lower extremity or abdominal aortic aneurysm; 51 (78%) patients were current or former smokers; and 16 (25%) had atrial fibrillation. The average growth rate of all aneurysms was 1.22 mm/y (SD, 1.93 mm). The mean surveillance time from initial diagnosis to last follow-up or intervention was 3.12 years (SD, 1.66 years). Of 87 aneurysms, 25 (29%) were repaired; 18 (21%) were repaired because of size criteria, 2 (2%) because of symptom criteria (claudication or acute limb ischemia), and 5 (6%) because of both criteria. During our study window, 62 aneurysms (71%) remained asymptomatic or did not undergo an intervention. The mean initial diameter at diagnosis was 16.9 mm (SD, 5.32 mm). Within the study, 50 (57%) aneurysms presented with or developed mural thrombus. Univariate analysis identified larger initial diameter (19.2 vs 14.7 mm; P = .020), atrial fibrillation (35% vs 16%; P = .042), and mural thrombus (38% vs 20%; P < .001) as predictors of diameter expansion greater than the mean. Multivariable analysis of the significant univariate factors determined that only initial diameter (odds ratio, 5.53; P = .007) and the presence or development of mural thrombus (odds ratio, 4.00; P = .008) maintained significance. CONCLUSIONS: Patients presenting with a PAA at 20 mm or >20 mm in diameter, presence of luminal thrombus, or atrial fibrillation may need to be observed at more frequent scanning intervals than those without these risk factors. Further studies are required to validate these predictive growth factors.


Assuntos
Aneurisma/epidemiologia , Artéria Poplítea , Trombose/epidemiologia , Idoso , Aneurisma/diagnóstico por imagem , Aneurisma/terapia , Doenças Assintomáticas , Distribuição de Qui-Quadrado , Comorbidade , Angiografia por Tomografia Computadorizada , Progressão da Doença , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/cirurgia , Estudos Retrospectivos , Fatores de Risco , Trombose/diagnóstico por imagem , Trombose/terapia , Fatores de Tempo , Ultrassonografia Doppler Dupla , Virginia/epidemiologia
18.
Cytopathology ; 28(6): 536-541, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28737285

RESUMO

OBJECTIVE: Endoscopic ultrasound-guided-fine needle aspiration (EUS-FNA) is an established first-line procedure in the management of solid and cystic pancreatic masses. Lymphoma is an uncommon diagnosis in EUS-FNA of the pancreas, and it is more common for such a diagnosis to be because of secondary involvement of the pancreas by a lymphoproliferative disorder than for this to represent isolated primary pancreatic lymphoma (PPL). We present the clinical, EUS and cytological features of these lesions. MATERIAL AND METHODS: After obtaining approval from our Institutional Review Board (IRB), nine cases of lymphoma diagnosed on EUS-FNA at a tertiary care cancer centre over a period of 8 years from 2008 to 2016 were retrieved from our endoscopy and pathology archives. Rapid onsite evaluation (ROSE) was carried out by a trained cytopathologist in all these cases. Cell blocks were available in seven cases, and immunophenotyping was performed on cell blocks using the immunoperoxidase method. Flow cytometry was performed in two cases. RESULTS: The most frequent site of involvement was the head of the pancreas (n=5, 55.6%). Four out of nine cases were diagnosed as PPL (44.4%). Five cases were diagnosed as lymphoma secondarily involving the pancreas (55.6%). The most frequent diagnosis was diffuse large B-cell lymphoma (n=6, 66.7%), followed by Hodgkin's lymphoma (n=2, 22.2%) and peripheral T-cell lymphoma (n=1, 11.1%). CONCLUSION: EUS-FNA in experienced hands is a valuable diagnostic modality, in conjunction with ROSE, immunohistochemistry and flow cytometry, in the diagnosis and sub-typing of both primary and secondary pancreatic lymphoma.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Linfoma Difuso de Grandes Células B/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Adolescente , Adulto , Idoso , Biópsia por Agulha Fina/métodos , Criança , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Feminino , Citometria de Fluxo/métodos , Humanos , Imuno-Histoquímica/métodos , Linfoma Difuso de Grandes Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Estudos Retrospectivos , Adulto Jovem
20.
J Cardiothorac Surg ; 12(1): 39, 2017 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-28535766

RESUMO

BACKGROUND: We introduce a novel preoperative anatomic severity grading system for acute type B aortic dissections and validate the system in a cohort of patients who underwent thoracic endovascular aortic repair. METHODS: We identified a cohort of patients who received thoracic endovascular aortic repair (TEVAR) for acute type B aortic dissection from 2008 to 2014. We developed an anatomic severity grading score (ASG) to measure attributes of aortic anatomy that we hypothesized may affect difficulty or durability of repair. Measurements were made using computed tomography angiography images and based on hypothesized severity, giving a potential score range of 0-38. RESULTS: We analyzed the computed tomography angiography images on a cohort of 30 patients with acute type B aortic dissection who underwent TEVAR. We created an area under the receiver operating characteristic curve (AUROC) using anatomic severity grading to predict aortic-related reinterventions. The AUROC was 0.72 (95% CI 0.39 to 1.1). Guided by the AUROC, we divided patients into two groups: a low-score group with anatomic severity grading scores <23 (n = 22), and a high-score group with scores ≥23 (n = 8). With this cutoff, anatomic severity grading exhibited 80% sensitivity and 84% specificity in predicting aortic-related reinterventions, with reinterventions in 50% of high-score patients and 4.5% of low-score patients (P = 0.011). The high score group also had significantly greater blood loss (200 vs 100 mL, P = 0.038), fluoroscopy time (36.0 vs 16.6 min; P = 0.022), and a trend for increased procedure time (164 vs 95 min; P = 0.083) than the low-risk group. Kaplan-Meier analysis revealed that the high-score group had a significantly decreased freedom from aortic-related reinterventions than the low-score group (38% vs 100% at 12-month followup; log rank P = 0.001). CONCLUSIONS: A preoperative anatomic severity grading score for acute type B aortic dissections consists of analysis of the proximal landing zone, curvature and tortuosity of the aorta, dissection anatomy, aortic branch vessel anatomy, and supraceliac aorta anatomy. Anatomic severity grading scores ≤23 are an excellent predictor of aortic-related reinterventions.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular/métodos , Procedimentos Endovasculares/métodos , Idoso , Dissecção Aórtica/diagnóstico , Aneurisma da Aorta Torácica/diagnóstico , Aortografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reoperação , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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