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1.
Environ Geochem Health ; 45(10): 6985-7010, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37578559

RESUMO

The article deals with the integrated and comprehensive study of the coal-bearing horizons from the South Karanpura Basin to delineate the biostratigraphy, palaeovegetation, palaeodepositional settings, and palaeoclimate in and around the investigated area during the deposition of Permian sediments. Highly diversified megafloral assemblages consist 13 genera and 72 species of order Glossopteridales, Cordaitales and Equisetales are documented among which 37 taxa are newly reported from Barakar and Raniganj formations of the area. Palynoassemblages-I and -II are recovered, which demonstrate the biostratigraphic age as Kungurian and Wordian-Capitanian, respectively. Overall the vegetation represents a luxuriant forest subjugated by arborescent deciduous trees bearing Glossopteris foliage with some conifers, cordaites, filicales, and peltaspermales. The biomarker study of the basin illustrates the unimodal distribution of n-alkanes in the sample set ranges from C14 to C29 which suggests major input from a single source of organic matter. The involvement of microbial activity and algal input is suggested for the basin. A relatively moderate-to-high water level condition can be inferred from elevated n-C25. The high CIA, PIA values and A-CN-K plot suggest intense weathering conditions in the source area. The source rocks are characterized by mature clayey type with abundant clay mineral, i.e., kaolinite. The current study portrays that the Permian climate was cooler in initial phase, which later on became warm temperate with high humidity. The palaeofloral entities and geochemical parameters suggest absolute diversification of Permian flora, the existence of continental freshwater setting in the vicinity and oxic to anoxic environment with fluctuating ground water conditions during the deposition of sediments.


Assuntos
Carvão Mineral , Água Subterrânea , Plantas , Tempo (Meteorologia) , Água
2.
COPD ; 18(3): 357-366, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33902371

RESUMO

The objective of this study is to estimate the excess economic burden of Asthma-COPD Overlap (ACO) among older adults in the United States. We used a cross-sectional study design with data from a nationally representative survey of Medicare beneficiaries (Medicare Current Beneficiary Survey) linked to Medicare fee-for-service claims. Older adults with ACO had higher average total healthcare expenditures ($45,532 vs. $12,743) and higher out-of-pocket spending burden (19% vs. 8.5%) compared to those with no-asthma no-COPD (NANC). Individuals with ACO also had almost two, and 1.5 times higher expenditures compared to individuals with asthma only and COPD only, respectively. Multivariable regression models indicated that the adjusted associations of ACO to economic burden remained positive and statistically significant. In comparison with NANC, nearly three-quarters of the excess total healthcare expenditures and 83% of the out-of-pocket spending burden of older adults with ACO were explained by differences in predisposing, enabling, need, personal healthcare practices, and external factors among the two groups. The higher number of unique medications and the increased incidence of fragmented care were the leading contributors to the excess economic burden among older adults with ACO comparing to NANC individuals. Interventions that reduce the number of medications and fragmented care have the potential to reduce the excess economic burden among older adults with ACO.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Idoso , Asma/epidemiologia , Estudos Transversais , Estresse Financeiro , Gastos em Saúde , Humanos , Medicare , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estados Unidos/epidemiologia
3.
J Environ Manage ; 277: 111362, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32949950

RESUMO

Submarine groundwater discharge (SGD) is an important process driven by marine and terrestrial forces. Low tide affects SGD the most, therefore the ideal time to detect SGD is the low tide, especially during spring tide. Techniques to detect and quantify SGD along with the understanding of the related aquifer characteristics is discussed in this study. Scientific community across the world is realizing the importance of studying and mapping SGD because in the scenario of climate change, this part of the global hydrological cycle is an important process and is known to have a significant effect on the marine ecosystem due to nutrient and metal inputs around the region of discharge. Therefore, understanding the processes governing SGD becomes very important. In this review, various components and processes related to SGD (e.g. Submarine Groundwater Recharge, Deep Porewater Upwelling, Recirculated Saline Groundwater Discharge), along with detailed discussion on impacts of SGD for marine ecosystem is presented. Also, it highlights the future research direction and emphasis is put on more research to be done keeping in mind the changing climate and its impacts on SGD.


Assuntos
Ecossistema , Água Subterrânea , Monitoramento Ambiental , Água do Mar , Navios
4.
J Anaesthesiol Clin Pharmacol ; 37(3): 395-401, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759550

RESUMO

BACKGROUND AND AIMS: Several factors determine the success of dural puncture. We aimed to assess the association of first puncture success and number of attempts with characteristics of the patient, provider, technique and equipment. MATERIAL AND METHODS: This prospective, observational study was performed in 1647 adult patients undergoing surgery under spinal anesthesia. Patient characteristics, anatomical landmarks, spinal bony deformity, provider experience, technique, skin punctures, needle redirections, subarachnoid space depth, and complications, if any, were noted. Difficult dural puncture was assessed by first puncture success and number of attempts (skin punctures plus needle redirections) required for successful needle placement. RESULTS: First puncture success was obtained in 872 (52.9%) patients. Failed dural puncture occurred in 4 (0.2%) of 1647 patients. Multivariate logistic regression analysis revealed that longer distance from C7 vertebral spine to tip of coccyx (P = 0.04), lower subarachnoid space depth (P = 0.001), good quality of bony landmarks (P = 0.001) and absence of crowded spine (P = 0.02) were associated with first puncture success. Male gender, poor or no spinal landmarks, presence of bony deformity and lower level of provider's experience predicted increased number of attempts for successful dural puncture. CONCLUSION: First puncture success of spinal block was influenced only by patient's anatomical factors, whereas the number of attempts required for successful block were predicted by both provider and patient factors.

5.
Biomed Chromatogr ; 34(1): e4742, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31749152

RESUMO

Quantitation of drugs used for the treatment of chronic lymphocytic leukemia in various biological matrices during both pre-clinical and clinical developments is very important, often in routine therapeutic drug monitoring. The first developed methods for quantitation were traditionally done on LC in combination with either UV or fluorescence detection. However, the emergence of LC with mass spectrometry in tandem in early 1990s has revolutionized the quantitation as it has provided better sensitivity and selectivity within a shorter run time; therefore it has become the choice of method for the analysis of various drugs. In this article, an overview of various bioanalytical methods (HPLC or LC-MS/MS) for the quantification of drugs for the treatment of chronic lymphocytic leukemia, along with applicability of these methods, is given.


Assuntos
Antineoplásicos , Cromatografia Líquida , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Antineoplásicos/análise , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Monitoramento de Medicamentos , Humanos , Espectrometria de Massas em Tandem
6.
J Environ Manage ; 244: 328-343, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31129465

RESUMO

The present study examines the spatial, seasonal and inter annual variation of biomass burning and its impact on regional aerosol optical properties over Northern India using multi-satellite aerosol observations: Active fire points, AOD (550 nm) and AE (550-860 nm) from MODIS retrievals during January 2003-December 2017 and AAOD (388 nm), SSA (388 nm) and AI from OMI UV retrievals during January 2005-December 2017. Results from MODIS active fire count statistics indicate an increase in the number of fire occurrences (average 1477 fires per year) over India in a period of 15 years (2003-2017). The dominant fire seasons are (i) Pre-monsoon (March to May) accounting to more than 45% and (ii) Post-Monsoon having 24% of total annual fires counts. However, the crop residue burning hotspot region located in Punjab and Haryana, constitutes 26% of the total fires in India. At an average, 15456 (77.08%) fire counts were reported during the paddy season, whereas 3296 (16.44%) fire counts during wheat season respectively. The crop residue burning over the northwest IGP (Punjab) significantly affect the aerosol optical properties locally as well in the downwind regions during post-monsoon season i.e., crop residue fires increased by 4% (170 fires per year) with corresponding AOD, AAOD & AI increased by 8%, 9% & 11% respectively. The satellite observation shows large gradient of aerosol parameters from north-west to south-east along the Himalayan foot-hills which indicates the regional transport of smoke aerosols over the region. This is also supported by ground based AOD observations at four locations (Patiala, Delhi, Dehradun and Kanpur) and Black Carbon measurements at two locations (Patiala and Dehradun). The climatological averaged values of ground based AOD550 for Patiala, Delhi, Dehradun and Kanpur are 0.52 ±â€¯0.26, 0.75 ±â€¯0.40, 0.45 ±â€¯0.24 and 0.57 ±â€¯0.29 respectively whereas BC concentrations are 8.43 ±â€¯3.14 µg m-3 & 3.36 ±â€¯1.26 µg m-3 for Patiala & Dehradun respectively. Comparison of MODIS derived AOD agrees well with ground based AODs (overall R = 0.86 and RMSE = 0.14). In addition, CALIPSO shows the maximum amount of biomass burning smoke aerosols present within the atmospheric boundary layer and some cases it extending up to 2-3 km altitudes. The smoke aerosol transport pathways originated from crop residue burning were analyzed using Hysplit forward trajectories. The results reveal that majority of smoke aerosols are transported to eastern IGP, central India and adjacent oceanic regions during post-monsoon season.


Assuntos
Poluentes Atmosféricos , Incêndios , Aerossóis , Biomassa , Monitoramento Ambiental , Índia , Estações do Ano
7.
J Biol Chem ; 292(2): 585-596, 2017 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-27913624

RESUMO

Eukaryotic ribosomes are composed of rRNAs and ribosomal proteins. Ribosomal proteins are translated in the cytoplasm and imported into the nucleus for assembly with the rRNAs. It has been shown that chaperones or karyopherins responsible for import can maintain the stability of ribosomal proteins by neutralizing unfavorable positive charges and thus facilitate their transports. Among 79 ribosomal proteins in yeast, only a few are identified with specific chaperones. Besides the classic role in maintaining protein stability, chaperones have additional roles in transport, chaperoning the assembly site, and dissociation of ribosomal proteins from karyopherins. Bcp1 has been shown to be necessary for the export of Mss4, a phosphatidylinositol 4-phosphate 5-kinase, and required for ribosome biogenesis. However, its specific function in ribosome biogenesis has not been described. Here, we show that Bcp1 dissociates Rpl23 from the karyopherins and associates with Rpl23 afterward. Loss of Bcp1 causes instability of Rpl23 and deficiency of 60S subunits. In summary, Bcp1 is a novel 60S biogenesis factor via chaperoning Rpl23 in the nucleus.


Assuntos
Núcleo Celular/metabolismo , Chaperonas Moleculares/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Ribossômicas/metabolismo , Subunidades Ribossômicas Maiores de Eucariotos/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Núcleo Celular/genética , Chaperonas Moleculares/genética , Proteínas Nucleares/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Proteínas Ribossômicas/genética , Subunidades Ribossômicas Maiores de Eucariotos/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética
8.
Breast Cancer Res Treat ; 167(1): 183-193, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28866828

RESUMO

PURPOSE: This study assessed the association between the severity of diabetes complications using diabetes complications severity index (DCSI) and stage of breast cancer (BC) at diagnosis among elderly women with pre-existing diabetes and incident BC. METHODS: Using Surveillance, Epidemiology and End Results-Medicare data, we identified women with incident BC during 2004-2011 and pre-existing diabetes (N = 7729). Chi-square tests were used to test for group differences in stage of BC at diagnosis. Multinomial logistic regression was used to examine the associations between the severity of diabetes complications and stage of BC at diagnosis. RESULTS: Overall, women with a DCSI = 2 and a DCSI ≥ 3 were more likely to be diagnosed at advanced stages as compared to those with no diabetes complications. In full adjusted association (after adding BC screening to the analysis model), the severity of diabetes complications was no longer an independent predictor of advanced stages at diagnosis. However, women with a DCSI = 2 were 26% more likely to be diagnosed at stage I (versus stage 0) of BC at diagnosis as compared to those without diabetes complications (OR 1.26, 95% CI 1.03-1.53). CONCLUSION: The increased likelihood of having advanced-stage BC at diagnosis associated with severity of diabetes-related complications appears to be mediated by lower rates of breast cancer screening among elderly women with pre-existing diabetes complications. Therefore, reducing disparity in receiving breast cancer screening among elderly women with diabetes may reduce the risk of advanced-stage breast cancer diagnosis.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Complicações do Diabetes/epidemiologia , Detecção Precoce de Câncer , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/complicações , Neoplasias da Mama/patologia , Complicações do Diabetes/patologia , Feminino , Humanos , Mamografia , Programas de Rastreamento , Medicare , Estadiamento de Neoplasias , Programa de SEER , Índice de Gravidade de Doença , Estados Unidos
9.
Microb Pathog ; 122: 130-136, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29909241

RESUMO

The recent global resurgence of arthritogenic alphaviruses, including Ross River, chikungunya, and dengue, highlights an urgency for the development of therapeutic strategies. Currently, dengue represents the most rapidly transmitting mosquito-borne viral disease worldwide. By contracting bone breaking diseases, patients experience devastating clinical manifestations involving muscle pain and bone loss. The bone self-repair and regeneration mechanisms can be damaged by the presence of viruses and bacteria. The rapid establishment of dengue epidemic and the severity of bacterial and viral infections affecting the bone stress the urgent need of developing effective interventions. Herein, we review current knowledge on bone breaking infections, covering both bacterial and mosquito-borne viral ones. The mechanisms exploited by these diseases to significantly affect the bone, including interferences with self-repair and regeneration routes, were discussed. In the final section, challenges for future research aimed to treat and prevent bacterial and mosquito-borne bone-breaking infections have been outlined.


Assuntos
Infecções Bacterianas/complicações , Fraturas Ósseas/fisiopatologia , Viroses/complicações , Animais , Humanos , Mosquitos Vetores/virologia
10.
J Natl Compr Canc Netw ; 16(6): 703-710, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29891521

RESUMO

Background: This study examined receipt of guideline-concordant care (GCC) according to evidence-based treatment guidelines and quality measures and specific types of treatment among older women with breast cancer. Patients and Methods: A total of 142,433 patients aged ≥66 years diagnosed with stage I-III breast cancer between 2007 and 2011 were identified in the SEER-Medicare linked database. Algorithms considering cancer characteristics and the appropriate course of care as per guidelines versus actual care received determined receipt of GCC. Multivariable logistic regression estimated the likelihood of GCC and specific types of treatment for women aged ≥75 versus 66 to 74 years. Results: Overall, 39.7% of patients received GCC. Patients diagnosed at stage II or III, with certain preexisting conditions, and of nonwhite race were less likely to receive GCC. Patients with hormone-negative tumors, higher grade tumors, and greater access to oncology care resources were more likely to receive GCC. Patients aged ≥75 years were approximately 40% less likely to receive GCC or adjuvant endocrine therapy, 78% less likely to have any surgery, 61% less likely to have chemotherapy, and about half as likely to have radiation therapy than those aged 66 to 74 years. Conclusions: Fewer than half of older women with breast cancer received GCC, with the lowest rates observed among the oldest age groups, racial/ethnic minorities, and women with later-stage cancers. However, patients with more aggressive tumor characteristics and greater access to oncology resources were more likely to receive GCC. Considering that older women have the highest incidence of breast cancer and that many are diagnosed at stages requiring more aggressive treatment, efforts to increase rates of earlier stage diagnosis and the development of less toxic treatments could help improve GCC and survival while preserving quality of life.


Assuntos
Neoplasias da Mama/terapia , Fidelidade a Diretrizes/estatística & dados numéricos , Avaliação de Processos e Resultados em Cuidados de Saúde/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Medicina Baseada em Evidências/normas , Medicina Baseada em Evidências/estatística & dados numéricos , Feminino , Humanos , Medicare/estatística & dados numéricos , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Qualidade de Vida , Programa de SEER/estatística & dados numéricos , Estados Unidos
11.
Lab Invest ; 97(10): 1167-1179, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28869589

RESUMO

Cardiovascular disease remains the leading cause of death and disability in advanced countries. Stem cell transplantation has emerged as a promising therapeutic strategy for acute and chronic ischemic cardiomyopathy. The current status of stem cell therapies for patients with myocardial infarction is discussed from a bioengineering and biomaterial perspective in this review. We describe (a) the current status of clinical trials of human pluripotent stem cells (hPSCs) compared with clinical trials of human adult or fetal stem cells, (b) the gap between fundamental research and application of human stem cells, (c) the use of biomaterials in clinical and pre-clinical studies of stem cells, and finally (d) trends in bioengineering to promote stem cell therapies for patients with myocardial infarction. We explain why the number of clinical trials using hPSCs is so limited compared with clinical trials using human adult and fetal stem cells such as bone marrow-derived stem cells.


Assuntos
Bioengenharia , Ensaios Clínicos como Assunto , Infarto do Miocárdio/terapia , Transplante de Células-Tronco , Animais , Materiais Biocompatíveis , Bioengenharia/métodos , Bioengenharia/tendências , Humanos , Camundongos , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/transplante , Pesquisa com Células-Tronco
12.
J Natl Compr Canc Netw ; 15(5): 578-587, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28476737

RESUMO

Background: Differences in Medicare expenditures during the initial phase of cancer care among rural and medically underserved elderly women with breast cancer (BC) and those from a nationally representative cohort have not been reported. The objective of this study was to determine Medicare expenditures during the initial phase of care among women in West Virginia (WV) who were Medicare beneficiaries with BC and compare them with national estimates. The magnitude of differences in these expenditures was also determined by using a linear decomposition technique. Methods: A retrospective observational study was conducted using the WV Cancer Registry-Medicare database and the SEER-Medicare database. Our study cohorts consisted of elderly women aged ≥66 years diagnosed with incident BC in 2003 to 2006. Medicare expenditures during the initial year after BC diagnosis were derived from all of the Medicare files. Generalized linear regressions were performed to model expenditures, after controlling for predisposing factors, enabling resources, need, healthcare use, and external healthcare environmental factors. Blinder-Oaxaca decomposition was conducted to examine the proportion of the differences in the average expenditures explained by independent variables included in the model. Results: Average Medicare expenditures for the WV Medicare cohort during the initial phase of BC care were $25,626 compared with $29,502 for the SEER-Medicare cohort; a difference of $3,876. In the multivariate regression, this difference decreased to $708 and remained significant. Only 16% of the differences in the average expenditures between the cohorts were explained by the independent variables included in the model. Enabling resources (6.86%), healthcare use (7.55%), and external healthcare environmental factors (3.33%) constituted most of the explained portion of the differences in the average expenditures. Conclusions: The difference in average Medicare expenditures between the elderly beneficiaries with BC from a rural state (WV) and their national counterparts narrowed but remained significantly lower after multivariate adjustment. The explained portion of this difference was mainly driven by enabling and healthcare use factors, whereas 84% of this difference remained unexplained.


Assuntos
Neoplasias da Mama/economia , Medicare/economia , Fatores Etários , Idoso , Região dos Apalaches , Estudos de Coortes , Feminino , Gastos em Saúde , Humanos , Estudos Retrospectivos , Estados Unidos
13.
J Natl Compr Canc Netw ; 15(11): 1401-1409, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29118232

RESUMO

Background: Understanding the patterns of healthcare utilization and costs during the initial phase of care (12 months after breast cancer [BC] diagnosis) in older women (aged ≥65 years) is crucial in the allocation of Medicare resources. The objective of this study was to determine healthcare utilization and costs during the initial phase of care in older, female, Medicare fee-for-service beneficiaries diagnosed with BC, and to determine the factors associated with higher costs. Methods: A retrospective observational study using the SEER-Medicare linked database was conducted in 69,307 women aged ≥66 years diagnosed with primary incident BC in 2003-2009 to determine healthcare utilization, average costs, and costs for specific services during the initial phase of care. Generalized linear model regression was conducted to identify the factors associated with higher costs in a multivariate framework. Results: A total of 96% of women were treated with surgery during the initial phase of BC care, whereas 21% and 54% underwent chemotherapy and radiotherapy, respectively. Costs during the initial phase of care totalled $28,075 in 2012 USD, comprising $13,344 for physician services and $7,456 for outpatient services. Factors associated with higher costs during the initial phase of care were younger age (66-69 years), African American race, higher household income, advanced stages of BC, initial BC treatment, higher number of primary care physician visits, and presence of comorbidities and/or a mental condition. Conclusions: The economic burden of BC is substantial during the initial phase of care. Physician and outpatient services accounted for the highest proportion of costs. Predisposing factors, need-related factors, healthcare use, and external environmental healthcare factors significantly predicted costs during the initial phase of care.


Assuntos
Neoplasias da Mama/terapia , Custos de Cuidados de Saúde/estatística & dados numéricos , Medicare/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/economia , Neoplasias da Mama/patologia , Planos de Pagamento por Serviço Prestado/economia , Planos de Pagamento por Serviço Prestado/estatística & dados numéricos , Feminino , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Humanos , Mastectomia/economia , Mastectomia/estatística & dados numéricos , Medicare/economia , Estadiamento de Neoplasias , Padrões de Prática Médica/economia , Radioterapia/economia , Radioterapia/estatística & dados numéricos , Estudos Retrospectivos , Programa de SEER/estatística & dados numéricos , Estados Unidos
14.
Nanomedicine ; 13(8): 2661-2669, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28800874

RESUMO

Minerals substituted apatite (M-HA) nanoparticles were prepared by the precipitation of minerals and phosphate reactants in choline chloride-Thiourea (ChCl-TU) deep eutectic solvent (DESs) as a facile and green way approach. After preparation of nanoparticles (F-M-HA (F=Fresh solvent)), the DESs was recovered productively and reprocess for the preparation of R-M-HA nanoparticles (R=Recycle solvent).The functional groups, phase, surface texture and the elemental composition of the M-HA nanoparticles were evaluated by advance characterization methods. The physicochemical results of the current work authoritative the successful uses of the novel (ChCl-TU) DESs as eco-friendly recuperate and give the medium for the preparation of M-HA nanoparticles. Moreover, the as-synthesized both M-HA nanoparticles exhibit excellent biocompatibility, consisting of cell co-cultivation and cell adhesion, in vivo according to surgical implantation of Wistar rats.


Assuntos
Regeneração Óssea , Osso e Ossos/lesões , Durapatita/uso terapêutico , Nanopartículas/uso terapêutico , Animais , Osso e Ossos/fisiologia , Linhagem Celular , Química Verde , Humanos , Masculino , Nanopartículas/ultraestrutura , Osteoblastos/metabolismo , Ratos Wistar , Rejuvenescimento
15.
Biomed Chromatogr ; 31(4)2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27632936

RESUMO

A highly sensitive, specific and enantioselective assay has been validated for the quantitation of OTX015 enantiomers [(+)-OTX015 and (-)-OTX015] in mice plasma on LC-MS/MS-electrospray ionization as per regulatory guidelines. Protein precipitation was used to extract (±)-OTX015 enantiomers and internal standard (IS) from mice plasma. The active [(-)-OTX015] and inactive [(+)-OTX015] enantiomers were resolved on a Chiralpak-IA column using an isocratic mobile phase (0.2% ammonia/acetonitrile 20 : 80, v/v) at a flow rate of 1.2 mL/min. The total run time was 6.0 min. (+)-OTX015, (-)-OTX015 and IS eluted at 3.34, 4.08 and 4.77 min, respectively. The MS/MS ion transitions monitored were m/z 492 → 383 for OTX015 and m/z 457 → 401 for IS. The standard curves for OTX015 enantiomers were linear (r2 > 0.998) in the concentration range 1.03-1030 ng/mL. The inter- and intraday precisions were in the range 2.20-13.3 and 8.03-12.1% and 3.80-14.4 and 8.97-13.6% for (+)-OTX015 and (-)-OTX015, respectively. Both the enantiomers were found to be stable in a battery of stability studies. This novel method has been applied to the study of stereoselective oral pharmacokinetics of (-)-OTX015 and unequivocally demonstrated that (-)-OTX015 does not undergo chiral inversion to its antipode in vivo in mice.


Assuntos
Acetanilidas/sangue , Acetanilidas/química , Cromatografia Líquida/métodos , Compostos Heterocíclicos com 3 Anéis/sangue , Compostos Heterocíclicos com 3 Anéis/química , Espectrometria de Massas em Tandem/métodos , Acetanilidas/administração & dosagem , Acetanilidas/farmacocinética , Administração Oral , Animais , Calibragem , Estabilidade de Medicamentos , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Masculino , Camundongos Endogâmicos BALB C , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray , Estereoisomerismo
16.
Biomed Chromatogr ; 31(2)2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27451018

RESUMO

A sensitive, specific and rapid LC-ESI-MS/MS method has been developed and validated for the quantification of epacadostat in mouse plasma using tolbutamide as an internal standard (IS) as per regulatory guidelines. Sample preparation was accomplished through a protein precipitation. Chromatographic separation was performed on an Atlantis dC18 column using a binary gradient using mobile phase A (acetonitrile) and B (0.2% formic acid in water) at a flow rate of 0.90 mL/min. Elution of epacadostat and IS occurred at ~2.41 and 2.51 min, respectively. The total chromatographic run time was 3.2 min. A linear response function was established in the concentration range of 1.07-533 ng/mL. The intra- and inter-day accuracy and precision were in the ranges of 1.81-12.9 and 3.80-11.1%, respectively. This novel method has been applied to a pharmacokinetic study in mice.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Inibidores Enzimáticos/sangue , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Oximas/sangue , Sulfonamidas/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Limite de Detecção , Masculino , Camundongos Endogâmicos BALB C , Espectrometria de Massas por Ionização por Electrospray/métodos
17.
Matern Child Health J ; 20(12): 2573-2580, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27465058

RESUMO

Objective The purpose of this study is to examine the burdens of caregivers on perception of the need and receipt of preventive dental care for a subset of children with special health care needs-children with Autism Spectrum disorder, developmental disability and/or mental health conditions (CASD/DD/MHC). Methods The authors used the 2009-2010 National Survey of CSHCN. The survey included questions addressing preventive dental care and caregivers' financial, employment, and time-related burdens. The associations of these burdens on perceptions and receipt of preventive dental care use were analyzed with bivariate Chi square analyses and multinomial logistic regressions for CASD/DD/MHC (N = 16,323). Results Overall, 16.3 % of CASD/DD/MHC had an unmet preventive dental care need. There were 40.0 % of caregivers who reported financial burden, 20.3 % who reported employment burden, and 10.8 % who reported time burden. A higher percentage of caregivers with financial burden, employment burden, and time-related burden reported that their CASD/DD/MHC did not receive needed preventive dental care (14.1, 16.5, 17.7 % respectively) compared to caregivers without financial, employment, or time burdens (9.0, 9.6 %, 11.0 % respectively). Caregivers with financial burden (adjusted multinomial odds ratio, 1.38 [95 % CI 1.02, 1.86] and employment burden (adjusted multinomial odds ratio, 1.45 [95 % CI 1.02, 2.06] were more likely to report that their child did not receive preventive dental care despite perceived need compared to caregivers without financial or employment burdens. Conclusions for practice Unmet needs for preventive dental care were associated with employment and financial burdens of the caregivers of CASD/DD/MHC.


Assuntos
Cuidadores/psicologia , Assistência Odontológica para Crianças/estatística & dados numéricos , Assistência Odontológica para a Pessoa com Deficiência/estatística & dados numéricos , Crianças com Deficiência/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Adolescente , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , Cuidadores/estatística & dados numéricos , Criança , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/psicologia , Feminino , Pesquisas sobre Atenção à Saúde , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Transtornos Mentais/diagnóstico , Saúde Bucal , Odontologia Preventiva , Fatores Socioeconômicos , Estados Unidos/epidemiologia
18.
Molecules ; 21(11)2016 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-27809259

RESUMO

In the present investigation, we prepared four different solvent fractions (chloroform, hexane, butanol, and ethyl acetate) of Moringa oleifera extract to evaluate its anti-inflammatory potential and cellular mechanism of action in lipopolysaccharide (LPS)-induced RAW264.7 cells. Cell cytotoxicity assay suggested that the solvent fractions were not cytotoxic to macrophages at concentrations up to 200 µg/mL. The ethyl acetate fraction suppressed LPS-induced production of nitric oxide and proinflammatory cytokines in macrophages in a concentration-dependent manner and was more effective than the other fractions. Immunoblot observations revealed that the ethyl acetate fraction effectively inhibited the expression of inflammatory mediators including cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor (NF)-κB p65 through suppression of the NF-κB signaling pathway. Furthermore, it upregulated the expression of the inhibitor of κB (IκBα) and blocked the nuclear translocation of NF-κB. These findings indicated that the ethyl acetate fraction of M. oleifera exhibited potent anti-inflammatory activity in LPS-stimulated macrophages via suppression of the NF-κB signaling pathway.


Assuntos
Acetatos/química , Regulação para Baixo/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Moringa oleifera/química , NF-kappa B/metabolismo , Extratos Vegetais , Transdução de Sinais/efeitos dos fármacos , Animais , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Células RAW 264.7
19.
W V Med J ; 112(5): 66-71, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29368489

RESUMO

Objectives: Tobacco-use is common among elderly lung cancer patients and continued tobacco-use can impact prognosis. This study evaluates patterns of receipt of Tobacco-use Cessation Counseling (TCC) services among these patients. Methods: Using West Virginia Cancer Registry-Medicare linked database (2004-2007), we identified elderly patients with lung cancer (n = 922) and categorized them by receipt of TCC services. Hierarchical generalized logistic model was constructed and survival outcomes were analyzed by Kaplan-Meier analysis, Log-Rank test, and Cox proportional hazards modeling. Results: Majority of patients (76.7%) received TCC services. Unadjusted analysis showed favorable survival outcomes in patients who received TCC services. However, adjusted lung cancer mortality risk was no different between the groups (HR (95% CI) = 1.78 (0.87-3.64)). Conclusion: This study highlights the critical need to address disparities in receipt of TCC services among elderly. Although lung cancer preventive services are covered under the Medicare program, underutilization of these services is a concern.


Assuntos
Envelhecimento , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Aconselhamento/estatística & dados numéricos , Neoplasias Pulmonares/mortalidade , Carcinoma de Pequenas Células do Pulmão/mortalidade , Fumar/efeitos adversos , Abandono do Uso de Tabaco/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/etiologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Masculino , Medicare/estatística & dados numéricos , Sistema de Registros , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/etiologia , Fumar/mortalidade , Estados Unidos , West Virginia/epidemiologia
20.
Lab Invest ; 95(1): 26-42, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25365202

RESUMO

Induced pluripotent stem cells (iPSCs) provide a platform to obtain patient-specific cells for use as a cell source in regenerative medicine. Although iPSCs do not have the ethical concerns of embryonic stem cells, iPSCs have not been widely used in clinical applications, as they are generated by gene transduction. Recently, iPSCs have been generated without the use of genetic material. For example, protein-induced PSCs and chemically induced PSCs have been generated by the use of small and large (protein) molecules. Several epigenetic characteristics are important for cell differentiation; therefore, several small-molecule inhibitors of epigenetic-modifying enzymes, such as DNA methyltransferases, histone deacetylases, histone methyltransferases, and histone demethylases, are potential candidates for the reprogramming of somatic cells into iPSCs. In this review, we discuss what types of small chemical or large (protein) molecules could be used to replace the viral transduction of genes and/or genetic reprogramming to obtain human iPSCs.


Assuntos
Células-Tronco Pluripotentes/citologia , Animais , Técnicas Genéticas , Humanos , Camundongos
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