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1.
Chemphyschem ; 24(24): e202300587, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-37880197

RESUMO

Studying the characteristics and molecular mechanisms of liquid self-diffusion coefficient and viscosity changes is of great significance for, e. g., chemical and petroleum processing. As examples of highly complex liquid,an asphaltene-free high-acid and high-viscosity crude oil and its extracted fractions were studied by comparing their 1 H DOSY diffusion maps. The crude oil exhibited a polydisperse diffusion distribution, including multiple diffusion portions with diffusion coefficients much smaller than that of any single fraction in independent diffusion. The main mechanism that leads to the decreases in the diffusion coefficients of crude oil is attributed to diffusion resistance enhanced by Dynamical Molecular-Interaction Networks (DMINs), rather than by enlargement of the diffusion species caused by molecular aggregation. Constructed through the synergistic interactions of various polar molecules in crude oil, DMINs dynamically bind polar molecules, trap polarizable molecules, and spatially hinder the free motion of non-polar molecules. Overall, this reduces the mobility of all molecular species, as illustrated by the decreased diffusion coefficients. This study demonstrates that DOSY is a powerful NMR method to investigate molecular motion abilities also in complex mixtures. In addition, the insights in the influence of the interaction matrix on the molecular mobility also help to understand the contribution of "structural viscosity" to the viscosity of heavy oil.

2.
J Med Chem ; 66(5): 3393-3410, 2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36891739

RESUMO

A series of autophagy-targeted antimetastatic clioquinol (CLQ) platinum(IV) conjugates were designed and prepared by incorporating an autophagy activator CLQ into the platinum(IV) system. Complex 5 with the cisplatin core bearing dual CLQ ligands with potent antitumor properties was screened out as a candidate. More importantly, it displayed potent antimetastatic properties both in vitro and in vivo as expected. Mechanism investigation manifested that complex 5 induced serious DNA damage to increase γ-H2AX and P53 expression and caused mitochondria-mediated apoptosis through the Bcl-2/Bax/caspase3 pathway. Then, it promoted prodeath autophagy by suppressing PI3K/AKT/mTOR signaling and activating the HIF-1α/Beclin1 pathway. The T-cell immunity was elevated by restraining the PD-L1 expression and subsequently increasing CD3+ and CD8+ T cells. Ultimately, metastasis of tumor cells was suppressed by the synergistic effects of DNA damage, autophagy promotion, and immune activation aroused by CLQ platinum(IV) complexes. Key proteins VEGFA, MMP-9, and CD34 tightly associated with angiogenesis and metastasis were downregulated.


Assuntos
Antineoplásicos , Clioquinol , Platina/farmacologia , Clioquinol/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Antineoplásicos/farmacologia , Apoptose , Autofagia , Linhagem Celular Tumoral
3.
Curr Med Res Opin ; 38(12): 2201-2208, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36205707

RESUMO

OBJECTIVE: In this study, we examined colorectal cancer (CRC) screening adherence in Medicare beneficiaries and associated healthcare resource utilization (HCRU) and Medicare costs. METHODS: Using 20% Medicare random sample data, the study population included Medicare fee-for-service beneficiaries aged 66-75 years on 1 January 2009, at average risk for CRC and continuously enrolled in Medicare Part A/B from 2008 to 2018. We excluded those who had undergone colonoscopy or flexible sigmoidoscopy during 2007-2008 and assumed everyone was due for screening in 2009; screening patterns were determined for 2009-2018. Based on US Preventive Services Task Force recommendations, individuals were categorized as adherent to screening, inadequately screened or not screened. HCRU and Medicare costs were calculated as mean per patient per year (PPPY). RESULTS: Of 895,846 eligible individuals, 13.2% were adherent to screening, 53.4% were inadequately screened, and 33.4% were not screened. Compared with those not screened, adherent or inadequately screened individuals were more likely to be female, White and have comorbidities. These individuals also used more healthcare services, generating higher Medicare costs. For example, physician visits were 14.6, 22.9 and 25.9 PPPY and total Medicare costs were $6102, $8469 and $9102 PPPY for those not screened, inadequately screened and adherent, respectively. CONCLUSIONS: In Medicare beneficiaries at average risk, adherence to CRC screening was low, although the rate might be underestimated due to lack of early Medicare data. The link between HCRU and screening status suggests that screening initiatives independent of clinical visits may be needed to reach unscreened or inadequately screened individuals.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Idoso , Humanos , Feminino , Estados Unidos , Masculino , Medicare , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Programas de Rastreamento , Aceitação pelo Paciente de Cuidados de Saúde
4.
BMC Health Serv Res ; 22(1): 1228, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36192728

RESUMO

BACKGROUND: While prevalence of up-to-date screening status is the usual reported statistic, annual screening incidence may better reflect current clinical practices and is more actionable. Our main purpose was to examine incident colorectal cancer (CRC) screening rates in Medicare beneficiaries and to explore characteristics associated with CRC screening. METHODS: Using 20% Medicare random sample data, the study population included 2016-2018 Medicare fee-for-service beneficiaries covered by Parts A and B aged 66-75 years at average CRC risk. For each study year, we excluded individuals who had a Medicare claim for a colonoscopy within 9 years, flexible sigmoidoscopy within 4 years, and multitarget stool DNA test (mt-sDNA) within 2 years prior; therefore, any observed screening during study year was considered an "incident screening". Incident screening rates were calculated as number of incident screenings per 1000 Medicare beneficiaries. Overall rates were normalized to 2018 Medicare population distributions of age, sex, and race. RESULTS: Each year, > 1.4 million individuals met the inclusion/exclusion criteria from > 6.5 million Medicare beneficiaries. The overall adjusted incident CRC screening rate per 1000 Medicare beneficiaries increased from 85.2 in 2016 to 94.3 in 2018. Incident screening rates decreased 11.4% (22.9 to 20.3) for colonoscopy and 2.4% (58.3 to 56.9) for fecal immunochemical test/guaiac-based fecal occult blood test; they increased 201.5% (6.5 to 19.6) for mt-sDNA. The 2018 unadjusted rate was 76.0 for men and 110.4 for women. By race/ethnicity, the highest 2018 rate was for Asian individuals and the lowest rate was for Black individuals (113.4 and 72.8, respectively). CONCLUSIONS: The 2016-2018 observed incident CRC screening rate in average-risk Medicare beneficiaries, while increasing, was still low. Our findings suggest more work is needed to improve CRC screening overall and, especially, among male and Black Medicare beneficiaries.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Idoso , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , DNA , Feminino , Guaiaco , Humanos , Masculino , Programas de Rastreamento , Medicare , Sangue Oculto , Aceitação pelo Paciente de Cuidados de Saúde , Estados Unidos/epidemiologia
5.
Reprod Sci ; 28(11): 3193-3199, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34085207

RESUMO

There is currently a dispute over the choice of ovulation induction treatment for infertile women with polycystic ovary syndrome (PCOS). The objective of this study is to compare the therapeutic effect of pulsed rhythmic administration protocol (PRAP) with conventional letrozole + human menopausal gonadotropin (HMG) in patients with clomiphene-resistance polycystic ovary syndrome (PCOS). A retrospective analysis of 821 intrauterine insemination (IUI) cycles between January 2015 and January 2020 was performed. Of these, 483 cycles were treated with a pulsed rhythmic administration protocol (PRAP), and 338 cycles were treated with conventional letrozole + HMG protocol (LHP). The therapeutic effect of the two protocols has been compared. The pregnancy rate was 18.07% in the LHP and 27.07% in the PRAP. The ongoing pregnancy rate in LHP was 14.46% and in PRAP was 22.73%. The research suggests that PRAP is more effective than LHP and could be an adequate ovulation induction strategy for the IUI cycle of patients with clomiphene-resistance PCOS.


Assuntos
Fármacos para a Fertilidade Feminina/administração & dosagem , Letrozol/administração & dosagem , Menotropinas/administração & dosagem , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/tratamento farmacológico , Taxa de Gravidez , Adulto , Inibidores da Aromatase/administração & dosagem , Clomifeno/administração & dosagem , Vias de Administração de Medicamentos , Resistência a Medicamentos/efeitos dos fármacos , Resistência a Medicamentos/fisiologia , Feminino , Seguimentos , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/epidemiologia , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/epidemiologia , Gravidez , Taxa de Gravidez/tendências , Estudos Retrospectivos , Adulto Jovem
6.
Environ Toxicol ; 36(6): 1181-1194, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33656234

RESUMO

Fenvalerate (Fen) is an endocrine disruptor, capable of interfering with the activity of estrogen and androgen. Our objective was to explore the molecular mechanisms of Fen on sperm in vivo. Adult male Sprague-Dawley rats were orally exposed to 0, 0.00625, 0.125, 2.5, 30 mg/kg/day Fen for 8 weeks. Sperm morphology, differential proteomics of sperm and testes, bioinformatic analysis, western blotting (WB), and RT-PCR were used to explore the mechanism of Fen on sperm. Data showed that low Fen doses significantly induced sperm malformations. In sperm proteomics, 47 differentially expressed (DE) proteins were enriched in biological processes (BPs) related to energy metabolism, response to estrogen, spermatogenesis; and enriched in cellular components (CCs) relating to energy-metabolism, sperm fibrous sheath and their outer dense fibers. In testicular proteomics, 56 DE proteins were highly associated with mRNA splicing, energy metabolism; and enriched in CCs relating to vesicles, myelin sheath, microtubules, mitochondria. WB showed that the expression of selected proteins was identical to their tendency in 2D gels. Literature indicates that key DE proteins in proteomic profiles (such as Trap1, Hnrnpa2b1, Hnrnpk, Hspa8, and Gapdh) are involved in P53-related processes or morphogenesis or spermatogenesis. Also, P53 mRNA and protein levels were significantly increased by Fen; bioinformatic re-analysis showed that 88.5% DE proteins and P53 formed a complex interacting network, and the key DE proteins were coenriched with P53-related BPs. Results indicate that key DE proteins of proteome underlying sperm malformations of rats exposed to low Fen doses are highly related to P53.


Assuntos
Proteoma , Proteína Supressora de Tumor p53 , Animais , Proteínas de Choque Térmico HSP90 , Masculino , Nitrilas , Proteômica , Piretrinas , Ratos , Ratos Sprague-Dawley , Espermatozoides
7.
J Bone Oncol ; 26: 100328, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33294317

RESUMO

BACKGROUND: Previous studies have quantified direct inpatient costs of skeletal-related events (SREs); however, costs associated with subsequent post-SRE care have not been examined. METHODS: We identified two study cohorts using 2011-2015 Medicare 20% sample data: patients diagnosed with 1) bone metastases from solid tumors or 2) multiple myeloma (MM), both with SRE-related hospitalization discharge dates January 1, 2011-September 30, 2015. We assessed discharge status and costs from discharge to the earliest of death, end of Medicare enrollment, or December 31, 2015. Discharge status was defined as: skilled nursing facility (SNF), rehabilitation facility, hospice, home health agency (HHA), long-term care (LTC) nursing home, LTC hospital, or rehospitalization within or after 30 days. Percentage, stay duration, and Medicare costs were calculated for each setting. All analyses were descriptive. RESULTS: We identified 7988 bone metastases patients and 4277 MM patients discharged from index SRE-related hospitalizations; corresponding mean ages were 76.9 and 76.6 years. The largest proportion of bone metastases patients were discharged to SNF (32.9%), then HHA (13.7%), hospice (13.5%), and LTC (11.3%); the pattern was similar for MM patients (SNF, 35.9%; HHA, 18.2%; hospice, 7.2%; LTC, 1.5%). Almost 10% of patients in both cohorts were re-hospitalized within 30 days. Mean Medicare cost per patient per facility stay was < $10,000 for hospice, and from $15,517 for LTC nursing home to $49,729 for LTC hospital for MM patients. CONCLUSION: Most elderly cancer patients (>75%) require healthcare facility support after SRE-related hospitalization, with substantial associated costs. Post-discharge management is clinically and economically important.

8.
Polymers (Basel) ; 12(10)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066175

RESUMO

Electret filters are widely used in particulate matter filtration due to their filtration efficiency that can be greatly improved by electrostatic forces without sacrificing the air resistance. However, the attenuation of the filtration efficiency remains a challenge. In this study, we report a novel strategy for producing an electret melt blown filter with superior filtration efficiency stability through a thermally stimulated charging method. The proposed approach optimizes the crystal structure and therefore results in the increased production probability of the charge traps. In addition, the re-trapping phenomenon caused by the thermal stimulation during the charging process can greatly increase the proportion of deep charge to shallow charge and improve the charge stability. A superior electret melt blown filtration material with a high filtration efficiency of 99.65%, low pressure drop of 120 Pa, and satisfactory filtration efficiency stability was produced after three cyclic charging times. The excellent filtration performance indicated that the developed material is a good air filtration candidate component for personal protection applications.

9.
Curr Med Res Opin ; 36(9): 1519-1527, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32715807

RESUMO

OBJECTIVE: To assess variations in hospitalizations, emergency department/observational (ED/OB) stays not resulting in hospitalization, reasons for hospitalization, and hospitalization discharge destinations after chemotherapy, information not provided as part of Oncology Care Model (OCM) baseline data. METHODS: OCM methodology was applied to the Medicare 20% sample data to identify 6-month patient episodes triggered by chemotherapy in 2012-2015. Proportions of episodes with hospitalization or ED/OB stays, reasons for hospitalization, and discharge destinations were summarized. RESULTS: Of 485,186 6-month episodes for 255,229 patients in 13,823 practices, 25% of episodes led to ≥1 hospitalization (from 14% in breast cancer to 56% in acute leukemia), and 23% to ED/OB stays (from 18% in breast cancer to 36% in liver cancer). In 2995 practices with ≥20 total episodes, practice-level proportions of episodes with hospitalization ranged from 14% to 31% (20th-80th percentile) and with ED/OB stays from 17% to 29%. For all cancers combined, the most frequent reasons for hospitalization were infection (13%), anemia (7%), dehydration (5%), and congestive heart failure (3%); the most common discharge destinations were home (71%) followed by a skilled nursing facility (13%), death (6%), and hospice (5%). Reasons for hospitalization and discharge destinations varied by cancer type; acute leukemia episodes led to the highest rates of infection and anemia, and central nervous system tumor episodes to the highest proportions of death or hospice discharge. CONCLUSION: The variations in frequency of and reasons for hospitalization, ED/OB stays, and hospitalization discharge destinations across cancer types should be considered when evaluating OCM practice performance.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Medicare , Neoplasias/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Estudos Retrospectivos , Estados Unidos
10.
Aliment Pharmacol Ther ; 51(11): 1149-1159, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32372515

RESUMO

BACKGROUND: Risk factors and timing associated with disease progression and mortality in nonalcoholic fatty liver disease (NAFLD) are poorly understood. AIMS: To evaluate the impact of disease severity, demographics and comorbidities on risk of mortality and time to progression in a large, real-world cohort of diagnosed NAFLD patients. METHODS: Claims data from a 20% Medicare representative sample between 2007 and 2015 were analysed retrospectively. Adults were categorised into disease severity groups: NAFLD/nonalcoholic steatohepatitis (NASH) alone, compensated cirrhosis, decompensated cirrhosis, liver transplant or hepatocellular carcinoma. Cumulative incidence of mortality and disease progression were calculated for each group and multivariate analyses performed adjusting for demographics, comorbidities and disease severity. RESULTS: A total of 10 826 456, patients were assessed and the prevalence of NAFLD was 5.7% (N = 621 253). Among patients with NAFLD, 71.1% had NAFLD/NASH alone and 28.9% had NAFLD cirrhosis. Overall, 85.5% of patients had hypertension, 84.1% dyslipidemia, 68.7% had cardiovascular disease and 55.5% diabetes. The cumulative risk of progression of NAFLD to cirrhosis, and compensated cirrhosis to decompensated cirrhosis was 39% and 45%, respectively, over 8 years of follow-up. The independent predictors of progression included cardiovascular disease, renal impairment, dyslipidemia and diabetes. The cumulative risk of mortality for NAFLD, NAFLD cirrhosis, decompensated cirrhosis and hepatocellular carcinoma was 12.6%, 31.1%, 51.4% and 76.2%, respectively. CONCLUSIONS: The present report (a) demonstrates that NAFLD is grossly underdiagnosed in real-world clinical settings and (b) provides new evidence on the progression rates of NAFLD and risk factors of mortality across the spectrum of severity of NAFLD and cirrhosis.


Assuntos
Cirrose Hepática/epidemiologia , Cirrose Hepática/patologia , Falência Hepática/epidemiologia , Falência Hepática/mortalidade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Adulto , Idoso , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/mortalidade , Estudos de Coortes , Comorbidade , Progressão da Doença , Feminino , Humanos , Cirrose Hepática/mortalidade , Falência Hepática/patologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/mortalidade , Masculino , Medicare/estatística & dados numéricos , Pessoa de Meia-Idade , Mortalidade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/mortalidade , Prevalência , Estudos Retrospectivos , Estados Unidos/epidemiologia
11.
Am J Gastroenterol ; 115(4): 562-574, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31833859

RESUMO

OBJECTIVES: As the prevalence of nonalcoholic steatohepatitis (NASH) in the elderly population increases, healthcare resource utilization (HCRU) and costs are also predicted to rise substantially. METHODS: This retrospective, observational cohort study used the Medicare 20% sample data set to evaluate the impact of NASH severity on HCRU and costs over 8 years (2007-2015). The sample included 255,681 patients with nonalcoholic fatty liver disease (NAFLD)/NASH: 185,407 (72.5%) with NAFLD/NASH and no further progression to advanced liver disease, 3,454 (1.3%) with compensated cirrhosis (CC), 65,926 (25.8%) with decompensated cirrhosis (DCC), 473 (0.2%) with liver transplant (LT), and 421 (0.2%) with hepatocellular carcinoma (HCC). RESULTS: Rates of comorbid diabetes, hypertension, hyperlipidemia, and cardiovascular disease were significantly higher in patients with CC or more severe liver disease compared with NAFLD/NASH and no progression. The annual mean number of all-cause healthcare visits increased from 32.1 for NAFLD/NASH with no progression to 37.3 for CC, 59.8 for DCC, 74.1 for LT, and 59.3 for HCC (P < 0.05). Total annual costs for inpatient, outpatient, physician, and pharmacy services rose from $19,908 in NAFLD/NASH with no progression to $129,276 for LT (P < 0.05). Generalized linear model adjusted for patient characteristics and comorbidities revealed that costs were 1.19, 3.15, 5.02, and 3.33 times significantly higher in patients diagnosed with CC, DCC, LT, or HCC, respectively, compared with NAFLD/NASH and no progression. DISCUSSION: These results confirm the substantial impact of NASH, particularly more severe disease, on HCRU and costs and identify patients who may benefit from interventions to prevent progression and subsequently reduce HCRU and costs.


Assuntos
Medicare , Hepatopatia Gordurosa não Alcoólica/terapia , Aceitação pelo Paciente de Cuidados de Saúde , Idoso , Comorbidade , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência , Estudos Retrospectivos , Índice de Gravidade de Doença , Estados Unidos/epidemiologia
12.
Nanoscale Res Lett ; 13(1): 379, 2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30470923

RESUMO

In this paper, a simple method to prepare hydrophilic reduced graphene oxide (rGO) was proposed via reducing GO by amino-terminated hyperbranched polymer (NHBP), the as-prepared NrGO could present excellent dispersibility, near infrared (NIR) light absorbance, photothermal conversion ability and stability. Then, the doxorubicin hydrochloride (DOX) was conjugated with NrGO to prepare the drug-loading system, and a pH/photothermal dual-responsive drug delivery behavior was characterized. At acidic environment or under NIR laser irradiation, the drug release rate could be improved, which is beneficial to control release anti-tumor drug in tumor tissues. What is more, the in vitro cell experiments revealed that NrGO was well biocompatible, and in the tumor inhibition part, comparing to the control group without any treatment, DOX@NrGO gained efficient chemo-photothermal synergetic therapy, the inhibition rate of which was much higher than single chemotherapy of released DOX. Therefore, the as-prepared DOX@NrGO obtained great potential application in tumor therapy and an excellent candidate in other biomed applications.

13.
Am J Nephrol ; 48(6): 447-455, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30472707

RESUMO

BACKGROUND: Most people with chronic kidney disease (CKD) are not aware of their condition. OBJECTIVES: To assess screening criteria in identifying a population with or at high risk for CKD and to determine their level of control of CKD risk factors. METHOD: CKD Health Evaluation Risk Information Sharing (CHERISH), a demonstration project of the Centers for Disease Control and Prevention, hosted screenings at 2 community locations in each of 4 states. People with diabetes, hypertension, or aged ≥50 years were eligible to participate. In addition to CKD, screening included testing and measures of hemoglobin A1C, blood pressure, and lipids. -Results: In this targeted population, among 894 people screened, CKD prevalence was 34%. Of participants with diabetes, 61% had A1C < 7%; of those with hypertension, 23% had blood pressure < 130/80 mm Hg; and of those with high cholesterol, 22% had low-density lipoprotein < 100 mg/dL. CONCLUSIONS: Using targeted selection criteria and simple clinical measures, CHERISH successfully identified a population with a high CKD prevalence and with poor control of CKD risk factors. CHERISH may prove helpful to state and local programs in implementing CKD detection programs in their communities.


Assuntos
Programas de Rastreamento/estatística & dados numéricos , Insuficiência Renal Crônica/diagnóstico , Adolescente , Adulto , Idoso , Centers for Disease Control and Prevention, U.S. , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Inquéritos Nutricionais/estatística & dados numéricos , Projetos Piloto , Prevalência , Avaliação de Programas e Projetos de Saúde , Insuficiência Renal Crônica/epidemiologia , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
14.
PLoS One ; 13(9): e0203767, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30256836

RESUMO

Whether and how anemia treatment with erythropoiesis stimulating agents (ESAs) before hemodialysis initiation may be associated with lower mortality after dialysis initiation is unknown. We compared all-cause and cardiovascular mortality in two groups of patients who experienced distinct anemia treatment patterns with ESAs before and after hemodialysis initiation. This retrospective cohort analysis included patients initiating hemodialysis April 1, 2012-June 30, 2013, identified from United States Renal Data System end-stage renal disease (ESRD) and pre-ESRD files. Patients treated with ESAs before and after hemodialysis initiation who maintained Hb ≥ 9.0 g/dL throughout (comparator group, n = 3662) were compared with patients with Hb < 9.0 g/dL before hemodialysis initiation (with or without ESAs) whose levels increased with ESAs after hemodialysis initiation (referent group, n = 4461). Cox proportional hazards models were used to calculate the hazard ratio of all-cause and cardiovascular mortality after hemodialysis initiation. Of 20,454 patients, 4855 (23.7%) had Hb < 9.0 g/dL upon hemodialysis initiation; of these 4855, 26.6% received ESAs before initiation. Comparator group Hb levels increased from 8.2 ± 0.8 mg/dL upon initiation to 10.9 ± 1.2 with ESAs afterward. Comparator patients were more likely than referent patients to be younger (76.3 ± 6.7 versus 77.2 ± 6.9 years), male (51.5% versus 49.8%), and black (24.6% versus 18.6%). Risk of all-cause mortality was lower for the comparator group versus the referent group at 3 (HR 0.83, 95% CI 0.68-1.00, P = 0.052), 6 (0.86, 0.74-1.00, P = 0.047), and 12 (0.88, 0.78-0.99, P = 0.036) months. The pattern was similar for cardiovascular mortality. Hb ≥ 9.0 with ESAs before and after hemodialysis initiation was generally associated with lower post-initiation all-cause and cardiovascular mortality compared with predialysis Hb < 9.0 g/dL in patients whose Hb levels subsequently improved with ESAs after hemodialysis initiation.


Assuntos
Anemia/terapia , Hematínicos/uso terapêutico , Diálise Renal , Idoso , Anemia/mortalidade , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos
15.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1061-1062: 421-429, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28818799

RESUMO

Thrombin (THR) plays a significant role in thromboembolic diseases, direct THR inhibitors are a class of important clinical anticoagulant drugs. This study established a THR in-solution based biospecific extraction combined with ultrafiltration and high performance liquid chromatography coupled with diode array detector and mass spectrometry analysis (TUA) method to screen and identify ligands for THR in Rhizoma Chuanxiong. After evaluating the reliability of the present TUA method using positive (argatroban) and negative (adenosine, tirofiban, ticagrelor) control drugs, this method was successfully applied to detect eight potential active compounds in Rhizoma Chuanxiong. Two new THR-targeted compounds isochlorogenic acid C and senkyunolide I with high THR inhibitory activity (IC50 206.48 and 197.23µM, respectively) were identified by liquid chromatography/mass spectrometry and enzyme inhibitory activity test finally. They were reported with direct THR inhibition activity for the first time and their ligand-THR interactions were explored by in silico molecular docking research. In addition, based on the TUA screening result, four compounds gained similar structure with the two hit compounds were also investigated as promising candidates targeting THR with high binding energy (>5.0kcal/mol). These results may prove that the proposed method could effectively screen THR inhibitors in complex mixtures.


Assuntos
Antitrombinas/análise , Cromatografia Líquida de Alta Pressão/métodos , Descoberta de Drogas/métodos , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas/métodos , Ultrafiltração/métodos , Antitrombinas/química , Antitrombinas/isolamento & purificação , Antitrombinas/metabolismo , Simulação de Acoplamento Molecular
16.
Huan Jing Ke Xue ; 37(10): 3870-3876, 2016 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-29964421

RESUMO

To understand the water quality problems caused by deposition and re-dissolution behaviors of residual aluminum in drinking water distribution system (DWDS), the effect of polysilicic acid on the deposition and re-dissolution behaviors of different aluminum species was investigated by using jar tests and quartz crystal microbalance, which could demonstrate the deposition behavior of different aluminum species and the physic-chemical properties of deposited layers. The results showed that the effect of polysilicic acid on the deposition behavior of different aluminum species was significant. Al0 (mainly monomeric species), Al13 and Al30 (polymeric species) could react rapidly with polysilicic acid, and some insoluble products formed. However, the stability of insoluble products from different aluminum species was distinct. The insoluble product formed by reaction of Al0 with polysilicic was relatively stable. With regard to the systems of polysilicic acid with Al13 and Al30, the dissolved aluminum concentration increased with reaction time, which indicated that the deposited product could be gradually transformed to soluble monomeric or oligomeric aluminum species. Compared with the influence of Al/Si ratio on Al0, the ratio of aluminum to silicon significantly affected the deposition and re-dissolution behavior of Al13 and Al30, and the re-dissolution rate of insoluble aluminum was the most rapid when the ratio of aluminum with silica was 0.2:20 (as mass ratio of Al to SiO2).

17.
Reprod Toxicol ; 51: 114-24, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25656793

RESUMO

Our objective was to explore molecular markers and mechanism of BDE47 on spermatogenesis in mammals. Adult male SD rats were gavaged daily with corn oil containing 0, 0.001, 0.03, 1 or 20mg BDE47/kg bw for eight weeks. Testes morphology was analyzed using electron microscopy, TUNEL, immunohistochemistry and morphometry. Differential proteome profile and western blotting were applied to determine molecular markers and protein expression. GC1-spg cells (mouse spermatogonial cells) were used to verify mechanism of BDE47. Data showed BDE47 reduced tubular epithelial thickness, impaired mitochondrial function and induced apoptosis in early leptotene spermatocytes. Proteomic study identified 70 differential spots corresponding to 64 proteins. 20 proteins related to apoptosis, 15 located in mitochondria. Exposure of GC1-spg cells showed BDE47 induced apoptosis, impaired mitochondria and decreased Bcl-2 in cells. Data indicate that BDE47 disrupts spermatogenesis, impairs mitochondrial function and induces apoptosis of early leptotene spermatocytes in rats probably via mitochondrial pathway.


Assuntos
Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/toxicidade , Espermatócitos/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Masculino , Camundongos , Microscopia Eletrônica de Transmissão , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteômica , Ratos Sprague-Dawley , Espermatócitos/ultraestrutura , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismo
18.
Magn Reson Chem ; 52(9): 486-90, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24975777

RESUMO

Polyvinylpyrrolidone (PVP) was used as a virtual stationary phase to separate p-xylene, benzyl alcohol, and p-methylphenol by the chromatographic NMR technique. The effects of concentration and weight-average molecular weight (Mw) of PVP, solvent viscosity, solvent polarity, and sample temperature on the resolution of these components were investigated. It was found that both higher PVP concentration and higher PVP Mw caused the increase of diffusion resolution for the three components. Moreover, the diffusion resolution did not change at viscosity-higher solvents. Moreover, the three components showed different resolution at different solvents. As temperature increased, the diffusion resolution between p-xylene and benzyl alcohol gradually increased, and the one between p-xylene and p-methylphenol slightly increased from 278 to 298 K and then decreased above 298 K. It was also found that the polarity of the analytes played an important role for the separation by affecting the diffusion coefficient.


Assuntos
Cromatografia/métodos , Espectroscopia de Ressonância Magnética/métodos , Povidona/química , Tetracloreto de Carbono , Difusão , Indicadores e Reagentes , Peso Molecular , Temperatura , Viscosidade
19.
Transplantation ; 98(5): 520-8, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-24825518

RESUMO

Although the United States possesses one of the most comprehensive transplant registries in the world, nationally representative data on how transplant care is structured and delivered is lacking. Therefore, we surveyed all 208 adult kidney transplant centers in the United States, excluding 37 pediatric and 58 inactive adult centers. Respondents were asked about the characteristics of their kidney transplant programs (25 items), the structure and process of care (18 items), coordination of care (10 items), and the characteristics of transplant physicians and surgeons (9 items). The survey was completed by directors of 156 transplant centers (75% response). The results demonstrated significant variation between centers in several domains. Sixty-five percent of transplant centers do not have a dedicated transplant pharmacist in outpatient care. Two thirds of transplant centers do not see the kidney transplant recipients at least monthly during the first year. Less than 30% of centers perform joint sit-down or walking rounds between nephrology and transplant surgery. There was significant variation in the structure and process of care in kidney transplantation. This implies variation in the use of resources at the transplant centers. This variation should be studied to determine best practices associated with optimal kidney allograft and patient survival.


Assuntos
Atenção à Saúde/organização & administração , Disparidades em Assistência à Saúde/estatística & dados numéricos , Transplante de Rim , Adulto , Estudos Transversais , Atenção à Saúde/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Humanos , Avaliação de Processos em Cuidados de Saúde , Estados Unidos
20.
Am J Kidney Dis ; 63(6): 997-1006, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24315770

RESUMO

BACKGROUND: Changes in anemia management practices due to concerns about erythropoiesis-stimulating agent safety and Medicare payment changes may increase patient risk of transfusion. We examined anemia management trends in hemodialysis patients and risk of red blood cell (RBC) transfusion according to dialysis facility-level hemoglobin concentration. STUDY DESIGN: Retrospective follow-up study; 6-month study period (January to June), 3-month exposure/follow-up. SETTING & PARTICIPANTS: For each year in 2007-2011, annual cohorts of point-prevalent Medicare primary payer patients receiving hemodialysis on January 1 with one or more hemoglobin measurements during the study period. Annual cohorts averaged 170,000 patients, with 130,000 patients and 3,100 facilities for the risk analysis. PREDICTOR: Percentage of facility patient-months with hemoglobin level<10 g/dL. OUTCOME: Patient-level RBC transfusion rates. MEASUREMENTS: Monthly epoetin alfa and intravenous iron doses, mean hemoglobin levels, and RBC transfusion rates; percentage of facility patient-months with hemoglobin levels<10 g/dL (exposure) and patient-level RBC transfusion rates (follow-up). RESULTS: Percentages of patients with hemoglobin levels<10 g/dL increased every year from 2007 (6%) to 2011 (~11%). Epoetin alfa doses, iron doses, and transfusion rates remained relatively stable through 2010 and changed in 2011. Median monthly epoetin alfa and iron doses decreased 25% and 43.8%, respectively, and monthly transfusion rates increased from 2.8% to 3.2% in 2011, a 14.3% increase. Patients in facilities with the highest prevalence of hemoglobin levels<10 g/dL over 3 months were at ~30% elevated risk of receiving RBC transfusions within the next 3 months (relative risk, 1.28; 95% CI, 1.22-1.34). LIMITATIONS: Possibly incomplete claims data; smaller units excluded; hemoglobin levels reported monthly for patients receiving epoetin alfa; transfusions usually not administered in dialysis units. CONCLUSIONS: Dialysis facility treatment practices, as assessed by percentage of patient-months with hemoglobin levels<10 g/dL over 3 months, were associated significantly with risk of transfusions in the next 3 months for all patients in the facility, regardless of patient case-mix.


Assuntos
Anemia/tratamento farmacológico , Anemia/epidemiologia , Transfusão de Eritrócitos/estatística & dados numéricos , Falência Renal Crônica/complicações , Idoso , Anemia/etiologia , Epoetina alfa , Eritropoetina/uso terapêutico , Feminino , Hematínicos/uso terapêutico , Hemoglobinas/análise , Humanos , Cobertura do Seguro , Falência Renal Crônica/terapia , Masculino , Medicare , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Diálise Renal , Estudos Retrospectivos , Medição de Risco , Estados Unidos
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