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1.
Eur Rev Med Pharmacol Sci ; 26(17): 6242-6250, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36111925

RESUMO

OBJECTIVE: Many clinical and imaging characteristics can influence the prognosis of multilevel cervical spondylotic myelopathy (M-CSM). This study investigated the factors that influence surgical outcomes among patients with M-CSM. PATIENTS AND METHODS: This prospective study included 30 patients who underwent surgical treatment for M-CSM from June 2019 to June 2021. RESULTS: The average age was 62.29 years, and the average follow-up time was 13.13 months. Preoperative, postoperative, and follow-up Modified Japanese Orthopaedic Association (mJOA) scores were 10.17, 13.53, and 16.17, respectively. The average postoperative and follow-up recovery rates were 45.46% and 76.69%, respectively. Patients older than 60 years (p = 0.04), male patients (p = 0.023), and smokers (p = 0.027) had lower preoperative mJOA scores than other groups. Patients with symptoms duration longer than 6 months had lower recovery rates (p = 0.021) than those with shorter symptom duration. Patients with intramedullary hyperintensity in ≤ 2 vertebra (p = 0.041) or anterior surgery (p = 0.022) had better postoperative recovery rates than their counterparts. A shorter period of hyperintensity in the intramedullary region on sagittal T2-weighted magnetic resonance imaging (T2W MRI) was significantly associated with faster discharge (p = 0.044). Patients with type 3 (discrete focal) hyperintensity in the intramedullary region on axial T2W MRI had a 6.75-fold increase in experiencing less than 50% postoperative recovery compared with other groups (odds ratio: 6.75, 95% confidence interval: 2.73-16.67). CONCLUSIONS: Good prognostic factors for a shorter recovery included hyperintensity in the intramedullary region for ≤ 2 levels, shorter period of hyperintensity in the intramedullary region on sagittal T2W MRI, and an anterior surgical approach. A duration of symptoms longer than 6 months and discrete hyperintensity in the intramedullary region on axial T2W MRI were poor prognostic indicators associated with a longer recovery period.


Assuntos
Doenças da Medula Espinal , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/cirurgia , Resultado do Tratamento
2.
Eur Cell Mater ; 42: 139-153, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34464450

RESUMO

Periodontitis is the most common inflammatory disease that leads to periodontal defects and tooth loss. Regeneration of alveolar bone and soft tissue in periodontal defects is highly desirable but remains challenging. A heparan sulphate variant (HS3) with enhanced affinity for bone morphogenetic protein-2 (BMP2) that, when combined with collagen or ceramic biomaterials, enhances bone tissue regeneration in the axial and cranial skeleton in several animal models was reported previously. In the current study, establishing the efficacy of a collagen/HS3 device for the regeneration of alveolar bone and the adjacent periodontal apparatus and related structures was sought. Collagen sponges loaded with phosphate-buffered saline, HS3, BMP2, or HS3 + BMP2 were implanted into surgically-created intra-bony periodontal defects in rat maxillae. At the 6 week end- point the maxillae were decalcified, and the extent of tissue regeneration determined by histomorphometrical analysis. The combination of collagen/HS3, collagen/BMP2 or collagen/HS3 + BMP2 resulted in a three to four-fold increase in bone regeneration and up to a 1.5 × improvement in functional ligament restoration compared to collagen alone. Moreover, the combination of collagen/HS3 + BMP2 improved the alveolar bone height and reduced the amount of epithelial growth in the apical direction. The implantation of a collagen/ HS3 combination device enhanced the regeneration of alveolar bone and associated periodontal tissues at amounts comparable to collagen in combination with the osteogenic factor BMP2. This study highlights the efficacy of a collagen/HS3 combination device for periodontal regeneration that warrants further development as a point-of-care treatment for periodontitis-related bone and soft tissue loss.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Regeneração Óssea , Colágeno , Heparitina Sulfato/farmacologia , Animais , Osso e Ossos , Osteogênese , Ligamento Periodontal , Ratos
3.
Int J Oral Maxillofac Surg ; 50(12): 1617-1627, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34229922

RESUMO

The purpose of this study was to report the outcomes of interpositional osteotomy with mineralized allograft in the treatment of alveolar vertical defects in preparation for implant placement. Thirteen defects (11 maxillary and two mandibular) were treated with osteotomy segments ranging in length from two to five missing teeth. The segments were positioned 5-7 mm coronally, with the gap space filled with allograft and then fixated with titanium hardware. Vertical bone augmentation was analyzed by superimposing pre- and post-surgical cone beam computed tomography images and stratified based on the length and number of missing teeth in each edentulous segment. The mean vertical bone gain was 3.7 ± 1.6 mm in the area of greatest vertical defect and the mean length of the transport segment was 20.5 ± 8.1 mm. These segments represented two-, three-, four-, or five-tooth edentulous sites; the mean vertical bone gain for these segments was 1.7 ± 0.5 mm, 3.8 ± 1.0 mm, 4.6 ± 0.9 mm, and 6.7 ± 0.0 mm, respectively. Stability of vertical height gain was found to be directly proportional to the span length of the osteotomy segment, with the largest five-tooth segment achieving the greatest gain. Vertical bone gain in two-tooth segments was minimal, indicating a moderate amount of resorption.


Assuntos
Aumento do Rebordo Alveolar , Maxila , Aloenxertos , Transplante Ósseo , Implantação Dentária Endóssea , Humanos , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Maxila/diagnóstico por imagem , Maxila/cirurgia , Osteotomia
4.
Diabet Med ; 38(5): e14396, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32876966

RESUMO

AIM: To examine the association between childhood food insecurity and incident diabetes. METHODS: Using health administrative databases linked to the Canadian Community Health Survey, we conducted a population-based cohort study of children aged <18 years from Ontario, Canada. Children without diabetes who had a household response to the Canadian Community Health Survey Household Food Security Survey Module were followed for a median of 9.5 years for incident diabetes. Multivariable Cox proportional hazards models were used to examine the association between childhood food insecurity and incident diabetes, adjusted sequentially for important clinical and socio-economic risk factors. RESULTS: We included 34 042 children, of whom 5.3% lived in food-insecure households. There were 184 new cases of diabetes, diagnosed at a median age of 16 and 18.5 years in food-secure and food-insecure children, respectively. In unadjusted analysis, childhood food insecurity was associated with an increased risk of incident diabetes (hazard ratio 1.69, 95% CI 1.01 to 2.81). When adjusted for clinical and socio-economic confounders, the relationship was no longer statistically significant (hazard ratio 1.55, 95% CI 0.91 to 2.66, adjusted for clinical confounders; hazard ratio 1.30, 95% CI 0.72 to 2.37, adjusted for clinical/socio-economic confounders). Our results remained robust in sensitivity analyses. CONCLUSIONS: Although food-insecure children are a medically and socially vulnerable population, they do not appear to be at increased risk of incident diabetes over a median of 9.5 years.


Assuntos
Diabetes Mellitus/epidemiologia , Insegurança Alimentar , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Diabetes Mellitus/etiologia , Características da Família , Feminino , Abastecimento de Alimentos/estatística & dados numéricos , Inquéritos Epidemiológicos , Humanos , Incidência , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Ontário/epidemiologia , Fatores de Risco , Determinantes Sociais da Saúde/estatística & dados numéricos , Fatores Socioeconômicos , Populações Vulneráveis/estatística & dados numéricos
5.
Fungal Syst Evol ; 6: 243-252, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32904240

RESUMO

Acacia mangium plantations account for more than 50 % of the exotic plantations in Vietnam. A new black butt symptom was discovered in 2012, followed by the wilting sign in Acacia seedlings in Tuyen Quang Province. Isolations recovered two Phytophthora species, the well-known Acacia pathogen P. cinnamomi, and an unknown species. The new species is described here as Phytophthora acaciivora sp. nov. Phylogenetically this species resides in clade 2d and is most closely related to P. frigida. Phytophthora acaciivora is a heterothallic species, oospores are aplerotic and antheridia are amphigynous. It produces predominantly elongated ovoid, semi papillate, persistent sporangia, no hyphal swellings and no chlamydospores. Optimum temperature for the growth is 25-30 °C and the maximum temperature is over 37.5 °C. Studies are underway to determine the impact of this new species on Acacia plantations in Vietnam.

6.
Neuropsychologia ; 146: 107550, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32619443

RESUMO

The spacing effect refers to the finding that, given a fixed amount of study time, a longer interval between study repetitions improves long-term retention (e.g., Cepeda et al., 2006; Ebbinghaus, 1885/1967; Melton, 1970). Although the spacing effect is a robust and reliable finding in the memory literature, its cognitive and neural mechanisms remain unclear. We used event-related potentials (ERPs) to investigate the neural correlates of the spacing effect in the context of the study-phase retrieval hypothesis, which posits that repeated exposure of an item serves as a reminder of one's previous experience with the item, thereby promoting long-term retention. ERPs were recorded from 30 healthy young adults as they studied pairs of words under three levels of lag, corresponding to 0, 4, or 12 intervening pairs between the first and second occurrences of a target pair. We used two study-phase tasks that differed in the degree of retrieval that was required. During the test phase, participants were tested on paired-associate recall. The results demonstrated a significant effect of spacing on memory performance. However, the effect of encoding task and the interaction between encoding task and spacing were not significant. The results of the partial least squares analyses, which are not constrained by time window or electrode selection, revealed a spacing effect on the ERP data for both study-phase tasks; this effect occurred late in the epoch and was most salient over the centro-parietal scalp region. The results add to the literature on the neural correlates of the spacing effect by providing a more comprehensive account compared to past ERP findings that were focused on testing specific ERP components. They also call for further investigation on the various theoretical accounts of the spacing effect.


Assuntos
Potenciais Evocados , Memória/fisiologia , Adolescente , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Rememoração Mental/fisiologia , Modelos Neurológicos , Fatores de Tempo , Adulto Jovem
7.
J Appl Microbiol ; 128(5): 1486-1496, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31834648

RESUMO

AIM: Studies on the anticancer effects of synbiotic fermented soymilk are rare. The aim of the present study was to evaluate the effect of synbiotic fermented soymilk supplemented with xylooligosaccharides and inoculated with Weissella cibaria FB069 (FSMXW) in the proliferation of colon cancer cell and compare it with the effect of soymilk inoculated with Lactobacillus rhamnosus GG (LGG). METHODS AND RESULTS: Both FB069 and LGG were able to grow in soy-based products and rapidly reduce their pH as a result of fermentation. The addition of XOS significantly enhanced the acidification rate, viscosity and total cell concentration in fermented soymilk inoculated with W. cibaria FB069. However, the same effect was not observed following inoculation with LGG. Moreover, the synbiotic FSMXW showed higher dextran, folate, GABA and aglycone content. FSMXW inhibited the proliferation of Caco-2 and HCT116 cell lines, by reducing the transcription of MD2, TLR4, MyD88, and NF-κb. CONCLUSIONS: The synbiotic soymilk containing XOS and W. cibaria FB069 increase nutrient and functional compounds through fermentation process. SIGNIFICANCE AND IMPACT OF THE STUDY: Our finding suggests that W. cibaria and XOS can be potentially employed in developing functional foods and health-related products.


Assuntos
Antineoplásicos/farmacologia , Glucuronatos , Oligossacarídeos , Leite de Soja , Simbióticos , Weissella/metabolismo , Reatores Biológicos , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Fermentação , Alimento Funcional/microbiologia , Glucuronatos/metabolismo , Células HCT116 , Humanos , Lacticaseibacillus rhamnosus/crescimento & desenvolvimento , Lacticaseibacillus rhamnosus/metabolismo , Oligossacarídeos/metabolismo , Leite de Soja/química , Weissella/crescimento & desenvolvimento
8.
Osteoporos Int ; 30(11): 2241-2248, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31410501

RESUMO

An electronic health record (eHR) review of Veterans with a spinal cord injury and disorder (SCI/D) was conducted to understand the extent to which Veterans Affairs (VA) providers pursue workups for secondary causes of osteoporosis in this population. Laboratory tests for secondary causes were ordered in only one-third of Veterans, with secondary causes identified in two-thirds of those tested, most frequently, hypogonadism and hypovitaminosis D. PURPOSE: To identify workups for secondary causes of osteoporosis in SCI/D and the extent to which subspecialty consultations are sought. METHODS: A total of 3018 prescriptions for an osteoporosis medication (bisphosphonate, calcitonin, denosumab, raloxifene, teriparatide) among 2675 Veterans were identified in fiscal years 2005-2015 from VA administrative databases. Approximately 10% of these prescriptions were selected for eHR review. RESULTS: eHR records of 187 Veterans with a SCI/D who had received pharmacological treatment for osteoporosis were reviewed. Workups for secondary causes of osteoporosis were performed in 31.5% of Veterans (n = 59) with approximately 64.4% of those tested (n = 38) having at least one abnormality. Hypogonadism (52.0% of those tested) and hypovitaminosis D (50.0% of those tested) were the most common secondary causes of osteoporosis identified in this population. Approximately 10% of primary care and SCI providers consulted subspecialists for further evaluation and treatment of osteoporosis. Endocrinologists more frequently performed a workup for secondary causes of osteoporosis compared to other provider specialties. CONCLUSIONS: Screening for secondary causes of osteoporosis, particularly for hypogonadism and hypovitaminosis D, should be considered in patients with a SCI/D.


Assuntos
Osteoporose/diagnóstico , Osteoporose/etiologia , Doenças da Medula Espinal/complicações , Traumatismos da Medula Espinal/complicações , Veteranos , Absorciometria de Fóton , Adulto , Idoso , Conservadores da Densidade Óssea/uso terapêutico , Técnicas de Laboratório Clínico , Registros Eletrônicos de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico , Encaminhamento e Consulta , Estados Unidos , United States Department of Veterans Affairs
9.
J Appl Microbiol ; 127(3): 778-793, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31211891

RESUMO

AIMS: Yeast and bacterial communities inhabit a sourdough starter to make artisanal bread. This study shows whether the interactions of micro-organisms derived from Australian sourdough starters provide some of the positive flavour, and aroma properties to bread by using defined sourdough cultures as the sole leaven in bread production. METHODS AND RESULTS: An investigation of Australian sourdough starters found that they contained Saccharomyces cerevisiae and Kazachstania exigua yeasts. When these yeasts were inoculated alone to ferment wheat flour in an extended fermentation, the bread had a heterogeneous crumb structure, a deeper colour and a distinctive chemical aroma profile than those made with commercial baker's yeast. When bread was made combining these yeasts individually and in combinations with lactic acid bacteria also isolated from these sourdough starters, including Lactobacillus plantarum, L. brevis, L. rossiae, L. casei, the bread aroma profiles and crumb structure were more distinctive, with compounds associated with sour aromas produced, and preferred by sensory panels. CONCLUSIONS: The use of defined mixed cultures as the leaven in bread making, by exploiting the microbial diversity of artisanal Australian starters, can produce bread with distinctive and attractive aromas. SIGNIFICANCE AND IMPACT OF THE STUDY: Understanding and identifying the community ecosystems found in sourdough cultures and using them as the sole leaven in bread production provide novel insights into microbial interactions and how they affect food quality by removing the effects of commercial yeast strains.


Assuntos
Pão/microbiologia , Técnicas de Cocultura , Tecnologia de Alimentos , Austrália , Fermentação , Farinha/microbiologia , Lactobacillales/isolamento & purificação , Lactobacillales/metabolismo , Lactobacillus plantarum/isolamento & purificação , Lactobacillus plantarum/metabolismo , Odorantes , Saccharomyces cerevisiae/isolamento & purificação , Saccharomyces cerevisiae/metabolismo , Saccharomycetales/isolamento & purificação , Saccharomycetales/metabolismo , Fermento Seco
10.
Opt Express ; 27(4): 5843-5850, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30876179

RESUMO

We report on the demonstration of an electrically injected AlGaN nanowire photonic crystal laser that can operate in the ultraviolet spectral range. The nanowire heterostructures were grown on sapphire substrate using a site-controlled selective area growth process. By exploiting the topological high-Q resonance of a defect-free nanowire photonic crystal, we have demonstrated electrically pumped lasers that can operate at 369.5 nm with a relatively low threshold current density of ~2.1 kA/cm2 under continuous wave operation at room-temperature. This work provides a promising approach for achieving low threshold semiconductor laser diodes operating in the UV spectral range that were previously difficult.

11.
J Appl Microbiol ; 126(6): 1861-1868, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30887606

RESUMO

AIMS: This study focuses on the development of a new strategy xylooligosaccharide (XOS) production from aqueous ammonia-pretreated rice straw (A-PRS), followed by ß-xylosidase hydrolysis produced by the newly identified strain Weissella cibaria FB069. METHODS AND RESULTS: We report a higher efficiency of A-PRS, including the removal of lignin and increase in cellulose and xylan content, compared to that of the alkali and stream explosion methods. Using the ammonia pretreatment method, rice straw was used to obtain 32·4% xylan. The crude xylanase from W. cibaria was used to hydrolyse A-PRS over different hydrolysis times. The highest XOS yield (131 mg XOS per gram rice straw) was observed after 10 h. XOS produced from the PRS was tested on stimulation effect on Bifidobacterium and Lactobacillus. CONCLUSION: The possibility of XOS production from PRS using ß-xylosidase with strong prebiotic properties. SIGNIFICANCE AND IMPACT OF THE STUDY: We investigated the new strain for signification production of XOS. The two-stage process here described could help to further explore the optimization conditions for prebiotic production. Additionally, the stimulation effect of XOS from alternative source has a promising prospect in functional food.


Assuntos
Amônia/química , Glucuronatos/metabolismo , Oligossacarídeos/metabolismo , Oryza/metabolismo , Prebióticos , Weissella/enzimologia , Xilosidases/metabolismo , Bifidobacterium/crescimento & desenvolvimento , Hidrólise , Lactobacillus/crescimento & desenvolvimento , Lignina/metabolismo
12.
Ultramicroscopy ; 187: 1-12, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29413406

RESUMO

A strain characterization technique based on Moiré interferometry in a scanning transmission electron microscope (STEM) and geometrical phase analysis (GPA) method is demonstrated. The deformation field is first captured in a single STEM Moiré hologram composed of multiple sets of periodic fringes (Moiré patterns) generated from the interference between the periodic scanning grating, fixing the positions of the electron probe on the sample, and the crystal structure. Applying basic principles from sampling theory, the Moiré patterns arrangement is then simulated using a STEM electron micrograph reference to convert the experimental STEM Moiré hologram into information related to the crystal lattice periodicities. The GPA method is finally applied to extract the 2D relative strain and rotation fields. The STEM Moiré interferometry enables the local information to be de-magnified to a large length scale, comparable to what can be achieved in dark-field electron holography. The STEM Moiré GPA method thus extends the conventional high-resolution STEM GPA capabilities by providing comparable quantitative 2D strain mapping with a larger field of view (up to a few microns).

13.
Lupus ; 27(1): 17-24, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28530467

RESUMO

Background The incidence of end stage renal disease (ESRD) in patients with systemic lupus erythematosus (SLE) is rising. However, the relationship between osteoporotic fractures and SLE in the setting of ESRD remains uninvestigated. The purpose of this study was to compare the frequency of incident osteoporotic fractures in patients with ESRD with and without SLE, to identify risk factors for fractures in patients with SLE and ESRD, and to examine the contribution of these fractures to mortality. Methods Retrospective cohort study of patients with SLE ( n = 716) and a 5% random sample of controls without SLE ( n = 4176) in the United States Renal Data System (USRDS) from years 2006-2008 enrolled in Medicare Part D. Results Fractures occurred in 10.6% ( n = 76) of patients with SLE and ESRD and 12.1% ( n = 507) of patients with ESRD without SLE ( p = 0.24). Older age (adjusted relative risk 1.02, 95% confidence interval 1.01-1.04) was associated with an increased risk for fracture in patients with SLE and ESRD. In multivariable analyses, vertebral and hip fractures more than doubled the risk for mortality. Conclusions The frequency of osteoporotic fractures in patients with SLE and ESRD is similar to the general population of patients with ESRD. Vertebral and hip fractures are significant contributors to mortality in patients with SLE and ESRD. Fracture prevention, in particular, for elderly patients with SLE and ESRD, should be considered. Summary SLE is not an independent risk factor for fractures in patients with ESRD. However, among patients with SLE and ESRD, vertebral and hip fractures are significant contributors to mortality.


Assuntos
Falência Renal Crônica/complicações , Lúpus Eritematoso Sistêmico/complicações , Fraturas por Osteoporose/etiologia , Sistema de Registros , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologia
14.
J Biomed Mater Res A ; 105(8): 2291-2298, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28445604

RESUMO

Many extracellular matrix proteins have positive influences on the adhesion, proliferation, and differentiation of stem cells into specific cell linages. Fibulin-1 (FBLN1), a member of a growing family of extracellular glycoproteins, contributes to the structure of the extracellular matrix. Here, we investigated the effect of FBLN1 on the ability of human nasal inferior turbinate-derived mesenchymal stem cells (hTMSCs) to undergo osteogenic differentiation. After we generated recombinant FBLN1, the characteristics of FBLN1-treated hTMSCs were evaluated using MTT assay, ALP and mineralization activities, and quantitative real-time PCR. FBLN1 significantly enhanced the adhesion activity (p < 0.001) and proliferation of hTMSCs (p < 0.05). The ALP and mineralization activities of cells were dramatically increased (p < 0.01) after 9 and 12 days of FBLN1 treatment, respectively. This indicated the ability of FBLN1 to induce hTMSCs to differentiate into osteoblasts. Furthermore, increasing the mRNA levels of osteogenic marker genes, such as a transcriptional coactivator with a PDZ-binding motif (TAZ), alkaline phosphatase (ALP), collagen type I (Col I), and osteocalcin (OCN), improved bone repair and regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2291-2298, 2017.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Células-Tronco Mesenquimais/citologia , Osteoblastos/citologia , Osteogênese , Conchas Nasais/citologia , Diferenciação Celular , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/metabolismo , Proteínas Recombinantes/metabolismo
15.
Leukemia ; 30(1): 190-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26202935

RESUMO

Currently available combination chemotherapy for acute myeloid leukemia (AML) often fails to result in long-term remissions, emphasizing the need for novel therapeutic strategies. We reasoned that targeted inhibition of a prominent nuclear exporter, XPO1/CRM1, could eradicate self-renewing leukemia-initiating cells (LICs) whose survival depends on timely XPO1-mediated transport of specific protein and RNA cargoes. Using an immunosuppressed mouse model bearing primary patient-derived AML cells, we demonstrate that selinexor (KPT-330), an oral antagonist of XPO1 that is currently in clinical trials, has strong activity against primary AML cells while sparing normal stem and progenitor cells. Importantly, limiting dilution transplantation assays showed that this cytotoxic activity is not limited to the rapidly proliferating bulk population of leukemic cells but extends to the LICs, whose inherent drug resistance and unrestricted self-renewal capacity has been implicated in the difficulty of curing AML patients with conventional chemotherapy alone.


Assuntos
Hidrazinas/farmacologia , Carioferinas/antagonistas & inibidores , Leucemia Mieloide Aguda/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Triazóis/farmacologia , Animais , Humanos , Terapia de Imunossupressão , Leucemia Mieloide Aguda/patologia , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína Exportina 1
16.
Intern Med J ; 45(12): 1306-10, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26444446

RESUMO

Corticosteroids are commonly used as co-analgesics with opioids for cancer pain; however limited quality data exist supporting their efficacy for this purpose. Further, little is known about individual prescribing practices. The current study surveyed members of the Australian New Zealand Society of Palliative Medicine about their use of corticosteroids as adjuvant analgesics in cancer pain. It confirmed high rates of utilisation and found variability in starting doses and associated decision-making. Further research is required to determine the efficacy and safety of corticosteroids as co-analgesics in cancer pain management.


Assuntos
Corticosteroides/administração & dosagem , Analgésicos Opioides/administração & dosagem , Neoplasias/complicações , Dor/tratamento farmacológico , Cuidados Paliativos/métodos , Padrões de Prática Médica/estatística & dados numéricos , Austrália/epidemiologia , Quimioterapia Combinada , Pesquisas sobre Atenção à Saúde , Humanos , Nova Zelândia/epidemiologia , Dor/etiologia , Medição da Dor
17.
Intern Med J ; 45(9): 898-904, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26332621

RESUMO

Chronic obstructive pulmonary disease (COPD) is a progressive, incurable illness, which leads to significant morbidity over long periods of time and mortality. Treatment aims to reduce symptoms, improve exercise capacity and quality of life, reduce exacerbations, slow disease progression and reduce mortality. However, breathlessness is common in patients with advanced COPD and remains undertreated. As all reversible causes of breathlessness are being optimally managed, consideration should be given to specific non-pharmacological and pharmacological treatment strategies for breathlessness. Low dose morphine has been shown to reduce safely and effectively breathlessness in patients with severe COPD and refractory dyspnoea. However, despite numerous guidelines recommending opioids in this clinical setting, many barriers limit their uptake by clinicians. Integration of palliative care earlier in the disease course can help to improve symptom control for people with severe COPD and refractory breathlessness. A multidisciplinary approach involving both respiratory and palliative care teams offers a new model of care for these patients.


Assuntos
Analgésicos Opioides/administração & dosagem , Dispneia/tratamento farmacológico , Morfina/administração & dosagem , Cuidados Paliativos/métodos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Progressão da Doença , Relação Dose-Resposta a Droga , Dispneia/etiologia , Dispneia/prevenção & controle , Dispneia/psicologia , Humanos , Equipe de Assistência ao Paciente , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Doença Pulmonar Obstrutiva Crônica/psicologia , Qualidade de Vida
18.
Int J Mol Sci ; 16(8): 19645-56, 2015 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-26295389

RESUMO

Fibronectin (FN) contributes to cell adhesion, proliferation, and differentiation in various cell types. To enhance the activity of fibronectin at the sites of focal adhesion, we engineered a novel recombinant fibronectin (FNIII10) fragment connected to the peptide amphiphile sequence (PA), LLLLLLCCCGGDS. In this study, the effects of FNIII10-PA on rat mesenchymal stem cells (rMSCs) were compared with those of FNIII10. FNIII10-PA showed the prominent protein adhesion activity. In addition, FNIII10-PA showed a significantly higher effect on adhesion, proliferation, and differentiation of rMSCs than FNIII10. Taken together, the FNIII10-containing self-assembled sequence enhanced rMSCs adhesion, proliferation, and differentiation.


Assuntos
Fibronectinas/farmacologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Engenharia de Proteínas/métodos , Animais , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Fibronectinas/química , Fibronectinas/genética , Masculino , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes de Fusão/farmacologia
19.
Int J Mol Sci ; 16(4): 7672-81, 2015 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-25853265

RESUMO

Integrin-mediated cell-matrix interactions play an important role in osteogenesis. Here, we constructed a novel osteoinductive fibronectin matrix protein (oFN) for bone tissue engineering, designed to combine the integrin-binding modules from fibronectin (iFN) and a strong osteoinductive growth factor, bone morphogenetic protein-2. Compared with iFN, the purified oFN matrix protein caused a significant increase in cell adhesion and osteogenic differentiation of pre-osteoblast MC3T3-E1 cells (p < 0.05).


Assuntos
Materiais Biocompatíveis/metabolismo , Proteína Morfogenética Óssea 2/metabolismo , Fibronectinas/metabolismo , Osteogênese , Animais , Adesão Celular , Diferenciação Celular , Camundongos , Osteoblastos/fisiologia , Engenharia Tecidual/métodos
20.
Spinal Cord ; 53(5): 402-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25622728

RESUMO

STUDY DESIGN: Retrospective review of a clinical database. OBJECTIVES: To examine treatment modalities of incident appendicular fractures in men with chronic SCI and mortality outcomes by treatment modality. SETTING: United States Veterans Health Administration Healthcare System. METHODS: This was an observational study of 1979 incident fractures that occurred over 6 years among 12 162 male veterans with traumatic SCI of at least 2 years duration from the Veterans Health Administration (VA) Spinal Cord Dysfunction Registry. Treatment modalities were classified as surgical or nonsurgical treatment. Mortality outcomes at 1 year following the incident fracture were determined by treatment modality. RESULTS: A total of 1281 male veterans with 1979 incident fractures met inclusion criteria for the study. These fractures included 345 (17.4%) upper-extremity fractures and 1634 (82.6%) lower-extremity fractures. A minority of patients (9.4%) were treated with surgery. Amputations and disarticulations accounted for 19.7% of all surgeries (1.3% of all fractures), and the majority of these were done more than 6 weeks following the incident fracture. There were no significant differences in mortality among men with fractures treated surgically compared with those treated nonsurgically. CONCLUSIONS: Currently, the majority of appendicular fractures in male patients with chronic SCI are managed nonsurgically within the VA health-care system. There is no difference in mortality by type of treatment.


Assuntos
Gerenciamento Clínico , Fraturas Ósseas/etiologia , Fraturas Ósseas/cirurgia , Traumatismos da Medula Espinal/complicações , Idoso , Doença Crônica , Fraturas Ósseas/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Traumatismos da Medula Espinal/epidemiologia , Estatísticas não Paramétricas , Estados Unidos , United States Department of Veterans Affairs , Veteranos
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