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Find video protocols related to scientific articles indexed in Pubmed.
Elementary Schoolteachers' Knowledge and Decision-making Regarding Dental Trauma.
Oral Health Prev Dent
PUBLISHED: 09-09-2014
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Purpose: To evaluate elementary schoolteachers' knowledge and decision making regarding dental trauma in Porto Alegre, Brazil. Materials and Methods: A questionnaire-based survey was conducted among elementary schoolteachers (n = 442). Questions encompassed sociodemographic characteristics and decision making regarding dental trauma. Data on the appropriate answer regarding what to do with a traumatised or avulsed tooth were analysed with multiple logistic regressions, adjusting for age, gender, work experience and previous training. Results: The study population consisted largely of women (90%), was 40 to 49 years old (44.3%) and had more than 15 years of work experience (56.6%). Women (OR = 2.68/p = 0.041), teachers under 30 years old (OR = 4.95/p = 0.041), those with more than 15 years of work experience (OR = 8.95/p < 0.001) or those who had already received previous dental trauma instructions (OR = 1.95/ p = 0.119) were more likely to choose the appropriate answer for an avulsion situation. Teachers under 30 years old (OR = 2.88/ p = 0.279), those with more than 15 years of work experience (OR = 4.55/p = 0.001) or those who had received previous training (OR = 3.39/p = 0.009) presented higher probabilites of choosing the appropriate answer for a crown fracture event. Conclusion: Greater work experience or previous instructions on how to approach dental trauma in the school environment were found to be major factors in schoolteachers' decision making regarding dental trauma.
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A pilot study of hypofractionated stereotactic radiation therapy and sunitinib in previously irradiated patients with recurrent high-grade glioma.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 08-04-2014
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Angiogenic blockade with irradiation may enhance the therapeutic ratio of radiation therapy (RT) through vascular normalization. We sought to determine the safety and toxicity profile of continuous daily-dosed sunitinib when combined with hypofractionated stereotactic RT (fSRT) for recurrent high-grade gliomas (rHGG).
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Secondary Analysis of RTOG 9508, a Phase 3 Randomized Trial of Whole-Brain Radiation Therapy Versus WBRT Plus Stereotactic Radiosurgery in Patients With 1-3 Brain Metastases; Poststratified by the Graded Prognostic Assessment (GPA).
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 04-22-2014
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Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary.
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EGFR expression and survival in patients given cetuximab and chemoradiation for stage III non-small cell lung cancer: a secondary analysis of RTOG 0324.
Radiother Oncol
PUBLISHED: 03-24-2014
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We investigated whether expression of epidermal growth factor receptor (EGFR) was associated with survival and disease control in this secondary analysis of a phase II trial of cetuximab+chemoradiation for stage III non-small cell lung cancer.
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A randomized trial of bevacizumab for newly diagnosed glioblastoma.
N. Engl. J. Med.
PUBLISHED: 02-21-2014
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Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the standard of care for patients with newly diagnosed glioblastoma. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, is currently approved for recurrent glioblastoma. Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known.
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PPAR-? agonist fenofibrate protects against the damaging effects of MPTP in a rat model of Parkinson's disease.
Prog. Neuropsychopharmacol. Biol. Psychiatry
PUBLISHED: 02-18-2014
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Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The etiology and pathogenesis of PD are still unknown, however, many evidences suggest a prominent role of oxidative stress, inflammation, apoptosis, mitochondrial dysfunction and proteosomal dysfunction. The peroxisome proliferator-activated receptor (PPAR) ligands, a member of the nuclear receptor family, have anti-inflammatory activity over a variety of rodent's models for acute and chronic inflammation. PPAR-? agonists, a subtype of the PPAR receptors, such as fenofibrate, have been shown a major role in the regulation of inflammatory processes. Animal models of PD have shown that neuroinflammation is one of the most important mechanisms involved in dopaminergic cell death. In addition, anti-inflammatory drugs are able to attenuate toxin-induced parkinsonism. In this study we evaluated the effects of oral administration of fenofibrate 100mg/kg 1h after infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the SNpc. First, we assessed the motor behavior in the open field for 24h, 7, 14 and 21 days after MPTP. Twenty-two days after surgery, the animals were tested for two-way active avoidance and forced swimming for evaluation regarding cognitive and depressive parameters, respectively. Twenty-three days after infusion of the toxin, we quantified DA and turnover and evaluated oxidative stress through the measurement of GSH (glutathione peroxidase), SOD (superoxide dismutase) and LOOH (hydroperoxide lipid). The data show that fenofibrate was able to decrease hypolocomotion caused by MPTP 24h after injury, depressive-like behavior 22 days after the toxin infusion, and also protected against decreased level of DA and excessive production of reactive oxygen species (ROS) 23 days after surgery. Thus, fenofibrate has shown a neuroprotective effect in the MPTP model of Parkinson's disease.
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Glucuronoarabinoxylan from coconut palm gum exudate: chemical structure and gastroprotective effect.
Carbohydr Polym
PUBLISHED: 02-06-2014
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A glucuronoarabinoxylan (CNAL) was extracted with 1% aq. KOH (25°C) from Cocos nucifera gum exudate. It had a homogeneous profile on HPSEC-MALLS-RI (Mw 4.6 × 10(4)g/mol) and was composed of Fuc, Ara, Xyl, GlcpA (and 4-O-GlcpA) in a 7:28:62:3 molar ratio. Methylation data showed a branched structure with 39% of non-reducing end units, 3-O-substituted Araf (8%), 3,4-di-O- (15%), 2,4-di-O- (5%) and 2,3,4-tri-O-substituted Xylp units (17%). The anomeric region of CNAL (13)C NMR spectrum contained 9 signals, indicating a complex structure. The main chain of CNAL was characterized by analysis of a Smith-degraded polysaccharide. Its (13)C NMR spectrum showed 5 main signals at ? 101.6, ? 75.5, ? 73.9, ? 72.5, and ? 63.1 that were attributed to C-1, C-4, C-3, C-2 and C-5 of (1?4)-linked ?-Xylp-main chain units, respectively. CNAL exhibited gastroprotective effect, by reducing gastric hemorrhagic lesions, when orally administered (1 and 3mg/kg) to rats prior to ethanol administration.
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Dose-response relationship with clinical outcome for lung stereotactic body radiotherapy (SBRT) delivered via online image guidance.
Radiother Oncol
PUBLISHED: 01-28-2014
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To examine potential dose-response relationships with various non-small-cell lung cancer (NSCLC) SBRT fractionation regimens delivered with online CT-based image guidance.
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Antidepressant-like effect of celecoxib piroxicam in rat models of depression.
J Neural Transm
PUBLISHED: 01-10-2014
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Beyond the current hypothesis of depression, several new biological substrates have been proposed for this disorder. The present study investigated whether the anti-inflammatory drugs celecoxib and piroxicam have antidepressant activity in animal models of depression. After acute administration, we observed antidepressant-like effects of celecoxib (10 mg/kg) and piroxicam (10 mg/kg) in the modified forced swim test in rats. Piroxicam increased serotonin and norepinephrine levels in the hippocampus. Prolonged (21-day) treatment with celecoxib (10 mg/kg) and piroxicam (10 mg/kg) rescued sucrose preference in a chronic mild stress model of depression. Additionally, the chronic mild stress-induced reduction of hippocampal glutathione was prevented by treatment with celecoxib and piroxicam. Superoxide dismutase in the hippocampus was increased after chronic mild stress compared with the non-stressed saline group. The non-stressed celecoxib and piroxicam groups and stressed piroxicam group exhibited an increase in hippocampal superoxide dismutase activity compared with the stressed saline group. Lipid hydroperoxide was increased in the stressed group treated with vehicle and non-stressed group treated with imipramine but not in the stressed groups treated with celecoxib and piroxicam. These results suggest that the antidepressant-like effects of anti-inflammatory drugs might be attributable to enhanced antioxidant defenses and attenuated oxidative stress in the hippocampus.
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Structural analysis of human 2'-O-ribose methyltransferases involved in mRNA cap structure formation.
Nat Commun
PUBLISHED: 01-10-2014
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The 5' cap of human messenger RNA contains 2'-O-methylation of the first and often second transcribed nucleotide that is important for its processing, translation and stability. Human enzymes that methylate these nucleotides, termed CMTr1 and CMTr2, respectively, have recently been identified. However, the structures of these enzymes and their mechanisms of action remain unknown. In the present study, we solve the crystal structures of the active CMTr1 catalytic domain in complex with a methyl group donor and a capped oligoribonucleotide, thereby revealing the mechanism of specific recognition of capped RNA. This mechanism differs significantly from viral enzymes, thus providing a framework for their specific targeting. Based on the crystal structure of CMTr1, a comparative model of the CMTr2 catalytic domain is generated. This model, together with mutational analysis, leads to the identification of residues involved in RNA and methyl group donor binding.
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Discrepancies in degree of conversion measurements by FTIR.
Braz Oral Res
PUBLISHED: 01-10-2014
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The purpose of this study was to evaluate the influence of the internal standard peak on the measured degree of conversion (DC) for methacrylate-based resins analyzed by Fourier-transform infrared spectroscopy (FTIR). The influence of different baseline measurement methods was also determined. Different blends were prepared, mixing BisGMA/BisEMA and BisGMA/TEGDMA at proportions of 0% to 100%, in weight. Camphoroquinone and ethyl-4-dimethylamino-benzoate were used to permit the light activation of blends. Degree of conversion was evaluated using FTIR equipped with an attenuated total reflectance (ATR) device. Samples were dispensed onto ATR crystal and light activated for 40 s. The DC was calculated by relating the height of the peak 1637 cm-1 to the intensity of different internal standard peaks (1715, 1608, or 1582 cm-1), measured using two different baseline methods, before and after polymerization. Data were compared by ANOVA at 5% significance. The relationship between DC and monomer ratio was obtained by regression analysis. Double-bond conversion ranged from 32.75% to 78.50% for BisGMA/BisEMA blends, and from 32.75% to 76.22% for BisGMA/TEGDMA blends. For the BisGMA/BisEMA blends, the DC showed a linear association with the composition of the comonomer blends, independent of the internal standard peak and baseline method used. In contrast, the trends in DC for BisGMA/TEGDMA blends were different for each method of measurement. The internal standard peaks and measurement baseline should be taken into account when using FTIR to calculate the DC of methacrylate-based resins, especially comonomer blends containing a high degree of monomers that lack aromatic rings.
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Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme.
J. Neurooncol.
PUBLISHED: 01-06-2014
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Retrospective data suggests that low serum glucose levels during the treatment of glioblastoma multiforme (GBM) may improve clinical outcomes. As such, many patients are implementing a ketogenic diet (KD) in order to decrease serum glucose flux while simultaneously elevating circulating ketones during radiation therapy and chemotherapy for the treatment of GBM. With IRB approval, a retrospective review of patients with high-grade glioma treated with concurrent chemoradiotherapy and adjuvant chemotherapy was carried out from August 2010 to April 2013. Serum glucose and ketone levels, dexamethasone dose, and toxicity of patients undergoing a KD during treatment were also assessed. Blood glucose levels were compared between patients on an unspecified/standard diet and a KD. Toxicity was assessed by Common Terminology Criteria for Adverse Events version 4. In total, 53 patients were analyzed. Six underwent a KD during treatment. The diet was well tolerated with no grade III toxicity and one episode of grade II fatigue. No episodes of symptomatic hypoglycemia were experienced. Four patients are alive at a median follow-up of 14 months. The mean blood glucose of patients on a standard diet was 122 versus 84 mg/dl for those on a KD. Based on this retrospective study, a KD appears safe and well tolerated during the standard treatment of GBM. Dietary restriction of carbohydrates through a KD reduces serum glucose levels significantly, even in conjunction with high dose steroids, which may affect the response to standard treatment and prognosis. Larger prospective trials to confirm this relationship are warranted.
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Vorinostat as a radiosensitizer for brain metastasis: a phase I clinical trial.
J. Neurooncol.
PUBLISHED: 01-02-2014
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Perform a phase I study to evaluate the safety, and tolerability of vorinostat, an HDAC inhibitor, when combined with whole brain radiation treatment (WBRT) in patients with brain metastasis. A multi-institutional phase I clinical trial enrolled patients with a histological diagnosis of malignancy and radiographic evidence of brain metastasis. WBRT was 37.5 Gy in 2.5 Gy fractions delivered over 3 weeks. Vorinostat was administrated by mouth, once daily, Monday through Friday, concurrently with radiation treatment. The vorinostat dose was escalated from 200 to 400 mg daily using a 3+3 trial design. Seventeen patients were enrolled, 4 patients were excluded from the analysis due to either incorrect radiation dose (n = 1), or early treatment termination due to disease progression (n = 3). There were no treatment related grade 3 or higher toxicities in the 200 and 300 mg dose levels. In the 400 mg cohort there was a grade 3 pulmonary embolus and one death within 30 days of treatment. Both events were most likely related to disease progression rather than treatment; nonetheless, we conservatively classified the death as a dose limiting toxicity. We found Vorinostat administered with concurrent WBRT to be well tolerated to a dose of 300 mg once daily. This is the recommended dose for phase II study.
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Somatic perception, cultural differences and immigration: results from administration of the Modified Somatic Perception Questionnaire (MSPQ) to a sample of immigrants.
Psychol Res Behav Manag
PUBLISHED: 01-01-2014
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The number of immigrants in Italy has doubled every 10 years from 1972 and Genoa hosts two large communities of immigrants from South America and Africa. We investigated differences in the somatic perception between immigrants and Italians and between South Americans and Africans living in the city of Genoa. During a 7 month period, an anonymous questionnaire asking for sociodemographic information and the Modified Somatic Perception Questionnaire (MSPQ) were administered to all immigrants accessing an outpatient clinic or the general practitioners offices. MSPQ mean scores were significantly higher in immigrant patients than in Italian patients, after adjusting for sex and age differences. We found no differences between South Americans and Africans in MSPQ score. The tendency to express discomfort through physical symptoms appears to be related to being a foreigner who arrived in Italy through a migratory trip and also to being a person who comes from a cultural context that is very different from the one of developed countries.
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Rhamnogalacturonan from Acmella oleracea (L.) R.K. Jansen: gastroprotective and ulcer healing properties in rats.
PLoS ONE
PUBLISHED: 01-01-2014
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A rhamnogalacturonan (RGal) isolated from Acmella oleracea (L.) R.K. Jansen administered by oral route showed gastroprotective activity against acute lesions induced by ethanol. In this study, we investigated the gastric ulcer healing effect of RGal and its mechanisms of action. Intraperitoneal treatment of animals with RGal protected the gastric mucosa against acute lesions induced by ethanol, with participation of gastric mucus. Furthermore, in the chronic ulcer model, oral administration of RGal accelerates the gastric ulcer healing, accompanied by increasing of cellular proliferation and gastric mucus content, reducing inflammatory parameters and oxidative stress. In addition, the repeated 7 days-treatment of animals with RGal did not show alterations of clinical and behavioral symptoms, body and organs weights or plasmatic biochemical parameters. Collectively, these results showed that RGal has an interesting antiulcerogenic activity and could constitute an attractive molecule of interest for the development of new antiulcer agents.
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Net clinical benefit analysis of radiation therapy oncology group 0525: a phase III trial comparing conventional adjuvant temozolomide with dose-intensive temozolomide in patients with newly diagnosed glioblastoma.
J. Clin. Oncol.
PUBLISHED: 10-07-2013
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Radiation Therapy Oncology Group trial 0525 tested whether dose-intensifying temozolomide versus standard chemoradiotherapy improves overall survival (OS) or progression-free survival (PFS) in newly diagnosed glioblastoma. Tests of neurocognitive function (NCF) and symptoms (using the MD Anderson Symptom Inventory-Brain Tumor module; MDASI-BT) and of quality of life (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ] -C30/BN20) examined the net clinical benefit (NCB) of therapy.
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Increased oxidative stress in prefrontal cortex and hippocampus is related to depressive-like behavior in streptozotocin-diabetic rats.
Behav. Brain Res.
PUBLISHED: 08-06-2013
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Depression is a common comorbid in diabetic patients. The pathophysiologic mechanisms that relate this comorbidity is not completely elucidated yet, although several lines of evidence point out that increased oxidative stress resulting from hyperglycemia may have a crucial role. Thus, the effect of prolonged treatment with insulin (INS), the antioxidant vitamin E (VIT E) or the antidepressant imipramine (IMI) was evaluated in animals submitted to forced swimming test. Oxidative stress parameters (lipid peroxidation product levels, reduced gluthatione levels and catalase and superoxide dismutase activities) were also evaluated in brain areas related to depression, prefrontal cortex (PFC) and hippocampus (HIP). Our data show that treatment of streptozotocin-induced diabetic (DBT) rats with INS (6UI/day, s.c.) prevented the blood glucose increase, reduced the immobility time, an antidepressant-like behavior, and normalized the reduced weight gain. Although the VIT E treatment (300mg/kg, p.o.) had not altered the blood glucose levels, this treatment was able to reduce the immobility time and to reestablish the reduced weight gain in DBT rats. Differently, treatment with IMI (15mg/kg, i.p.) induced antidepressant-like behavior in normoglycemic besides DBT animals. While VIT E and IMI treatments restored only specific oxidative stress parameters, INS was able to prevent all changed parameters evaluated in both PFC and HIP from DBT animals. Therefore, our data provide further evidence of the importance of oxidative stress in PFC and HIP in the pathophysiology of depression related to diabetes.
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Identification of a KRAS mutation in a patient with non-small cell lung cancer treated with chemoradiotherapy and panitumumab.
Cancer Biol. Ther.
PUBLISHED: 08-02-2013
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RTOG 0839 is a Phase II study of pre-operative chemoradiotherapy with or without panitumumab in potentially operable locally advanced non-small cell lung cancer (NSCLC). The investigational agent, panitumumab, is an anti-epithelial growth factor receptor (EGFR) antibody that improves progression-free survival in chemorefractory metastatic colorectal cancer (mCRC). Recently, both KRAS mutational status (i.e., mutated or not) and subtype (i.e., activating or inactivating) have been shown to be predictive of response to anti-EGFR therapy in mCRC. However, in NSCLC, it is unknown if KRAS mutational status or subtype predict benefit to anti-EGFR therapies because of unique genetic and epigenetic factors unique to each cancer. We present a patient with stage III NSCLC containing a KRAS G12D activating mutation who had a partial pathologic response, with disappearance of a minor KRAS mutant clone. This case suggests possible eradication of the G12D KRAS lung cancer clones by concurrent chemoradiation with panitumumab.
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Polysaccharides from prunes: gastroprotective activity and structural elucidation of bioactive pectins.
Food Chem
PUBLISHED: 06-21-2013
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Prunes are the dried fruits from Prunus domestica. After the purification steps, two homogeneous polysaccharides were characterised, SF-50R and SF-50E and contained Ara:Gal:Rha:GalA in 47.8:31.5:10.7:10.0 and 39.6:50.3:5.1:5.0 molar ratios, respectively. Methylation analysis and (13)C NMR spectroscopy indicated that both fractions are constituted by rhamnogalacturonans with type I arabinogalactans as side chains, differing mainly in the proportions of the rhamnogalacturonan backbone, in the length of the (1?4)-?-galactan chain and in the proportion of the arabinan side chain. Crude water extract (PWH) and fraction SF-50E were evaluated for their gastroprotective properties against ethanol-induced acute gastric lesions in rats. Oral administration of PWH (3 and 10mg/kg) reduced the gastric lesion area by 67±11% and 60±12%, respectively, while fraction SF-50E (10 and 30mg/kg) inhibited the lesion area by 84±12% and 83±12%, respectively. These results indicated that prunes polysaccharides act as gastroprotective agents in rats.
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Reduced-dose fractionated stereotactic radiotherapy for acoustic neuromas: maintenance of tumor control with improved hearing preservation.
Neurosurgery
PUBLISHED: 06-13-2013
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Fractionated stereotactic radiotherapy (FSRT) is a noninvasive treatment for acoustic neuromas (ANs). Initial reports from our institution demonstrated that the reduction of treatment dose to 46.8 Gy resulted in improved preservation of functional hearing status.
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Antinociceptive effects of ethanolic extract from the flowers of Acmella oleracea (L.) R.K. Jansen in mice.
J Ethnopharmacol
PUBLISHED: 06-07-2013
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In Brazil, Acmella oleracea (L.) R.K. Jansen, popularly known as "jambu", has been used by some communities from Amazon region to treat toothache. In this study we examined the antinociceptive effect of the ethanolic extract obtained from the flowers of Acmella oleracea (EEAO) in animal models of nociceptive (chemical and thermal) and neuropathic (partial sciatic nerve ligation) pain.
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PI3K Pathway in Gynecologic Malignancies.
Am Soc Clin Oncol Educ Book
PUBLISHED: 05-30-2013
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Alterations in PI3K signaling are common in gynecologic malignancies. Alterations detected vary with gynecologic cancer type, histologic subtypes within these, and clinical phenotypes. The distinction into type I and type II endometrial and ovarian carcinomas is reflected in distribution of changes detected in several of the PI3K members. PIK3CA mutations and amplifications are common in endometrial, ovarian, and cervical cancers. PTEN mutations and deletions are frequent in endometrial cancers. Several immunohistochemical studies of protein expression have explored these and other potential surrogate markers for PI3K pathway activation. Biomarkers to measure level of PI3K activity in clinical samples are not established. Whether amplifications, mutations, and deletions of the PI3K pathway members, and in particular change in their expression levels, result in clinically relevant pathway activation needs to be further explored. Also, to what extent these alterations drive the tumor behavior and are critical targets for therapeutics to improve patient survival needs to be further tested to establish predictive biomarkers for response to PI3K inhibition.
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Antiulcer and gastric antisecretory effects of dichloromethane fraction and piplartine obtained from fruits of Piper tuberculatum Jacq. in rats.
J Ethnopharmacol
PUBLISHED: 04-02-2013
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Piper tuberculatum Jacq. (Piperaceae) is medicinally used as an analgesic and as a treatment for gastric complaints. Thus, the current study aimed to investigate the gastroprotective and antisecretory properties of the dichloromethane fraction of the fruit of Piper tuberculatum (DFPT) and piplartine, a compound isolated from the DFPT, in rats.
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Structure of a galactoarabinoglucuronoxylan from tamarillo (Solanum betaceum), a tropical exotic fruit, and its biological activity.
Food Chem
PUBLISHED: 03-01-2013
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Tamarillo (Solanum betaceum) is a tropical exotic fruit whose polysaccharides were extracted from the ripe pulp. After various purification steps, homogeneous fractions (designated PTW, STK-1000R and PF) were analyzed by sugar composition, HPSEC, methylation and NMR spectroscopy analysis. The results showed that the fraction PTW consisted of a linear arabinan with (1?5)-linked ?-l-arabinofuranosyl units. Fractions designated as STK-1000R and PF contained galactoarabinoglucuronoxylans, with (1?4)-linked ?-d-Xylp residues in the backbone, carrying branches exclusively at O-2. The polysaccharide in STK-1000R is less branched than that in the PF fraction (?20.0% and 36.5%, respectively), with side-chains formed by (1?5)-linked ?-l-Araf residues and (1?4)-linked ?-d-GlcpA residues and with non-reducing end units formed by ?-l-Araf, ?-Arap, ?-d-Galp, ?-d-GlcpA and 4-O-Me-?-d-GlcpA. Intraperitoneal administration of the STK-1000R fraction in mice significantly reduced the number of abdominal constrictions induced by 0.6% acetic acid and the inflammatory phase of nociception induced by 2.5% formalin, indicating that that fraction has an antinociceptive effect on inflammatory pain models.
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ALK inhibitor PF02341066 (crizotinib) increases sensitivity to radiation in non-small cell lung cancer expressing EML4-ALK.
Mol. Cancer Ther.
PUBLISHED: 02-26-2013
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Crizotinib (PF02341066) is a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that has been shown to selectively inhibit growth of cancer cells that harbor the EML4-ALK fusion found in a subset of patients with non-small cell lung cancer (NSCLC). While in clinical trials, PF02341066 has shown a significant therapeutic benefit as a single agent; the effectiveness of combining it with other therapeutic modalities including ionizing radiation remains unknown. To further elucidate the role of PF02341066 in tumor inhibition, we examined its effects alone and in combination with radiation on downstream signaling, apoptosis, and radiosensitivity in two NSCLC cell lines in vitro: H3122, which harbors the EML4-ALK fusion, and H460, which does not. We also examined the in vivo effects of PF02341066 in H3122 mouse xenografts. In the H3122 cell line, PF02341066 inhibited phosphorylation of ALK and its downstream effectors: AKT, ERK, and STAT3. H3122 cells treated with a combination of PF02341066 and radiation showed an increase in cellular apoptosis and were sensitized to radiation therapy (dose enhancement ratio, 1.43; P < 0.0001). Moreover, in an H3122 xenograft model, the combined treatment resulted in greater tumor growth inhibition than either treatment alone (P < 0.05). None of these effects was observed in the EML4-ALK-negative H460 cells. Our findings indicate that PF02341066 acts as a radiation sensitizer in cells harboring the EML4-ALK fusion, providing a rationale for a clinical trial combining ALK inhibitor with radiation in the NSCLCs expressing ALK.
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A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: Radiation Therapy Oncology Group 0320.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-04-2013
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A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS.
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Decline in tested and self-reported cognitive functioning after prophylactic cranial irradiation for lung cancer: pooled secondary analysis of Radiation Therapy Oncology Group randomized trials 0212 and 0214.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 01-23-2013
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To assess the impact of prophylactic cranial irradiation (PCI) on self-reported cognitive functioning (SRCF), a functional scale on the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30).
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Chemical and biological characterization of polysaccharides isolated from Ilex paraguariensis A. St.-Hil.
Int. J. Biol. Macromol.
PUBLISHED: 01-02-2013
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The potential gastroprotection of polysaccharides (SP) isolated from maté (Ilex paraguariensis) leaves of different growth stages, under different sunlight conditions and of processing methods were evaluated. The SP consist of type I arabinogalactan (AG1) containing a (1?4)-linked ?-Galp chain, with substituents of arabinosyl units at O-6. This arabinogalactan seems to be attached to rhamnosyl units from a RG1, via 1?4 linkage. Oral administration of SP1, SP9, SP10, SP11 and SP12 inhibited the gastric lesions induced by ethanol in rats. Altogether, the present data indicate the therapeutic role of maté polysaccharides against gastric lesion and propose its use or of its crude plant extract as a phytotherapic medicine.
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The addition of nanostructured hydroxyapatite to an experimental adhesive resin.
J Dent
PUBLISHED: 01-02-2013
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Was produced nanostructured hydroxyapatite (HAnano) and evaluated the influence of its incorporation in an adhesive resin.
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Antinociception of ?-D-glucan from Pleurotus pulmonarius is possibly related to protein kinase C inhibition.
Int. J. Biol. Macromol.
PUBLISHED: 09-15-2011
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?-D-Glucan, a polysaccharide isolated from an edible mushroom Pleurotus pulmonarius (Fr.) Quel., presented antinociceptive activity in mice. This study evaluated the involvement of transient receptor potential (TRP) channels and protein kinase C (PKC) on antinociceptive effect of a (1?3),(1?6)-linked ?-D-glucan (GL) in mice. Intraperitoneal administration of GL potently inhibited nociceptive responses induced by intraplantar injections of capsaicin, cinnamaldehyde, menthol, acidified saline and phorbol myristate acetate (PMA). Moreover, Western blot analysis revealed that GL treatment also prevented PMA-induced PKC? activation. Collectively, present results demonstrate that GL could constitute an attractive molecule of interest for the development of new analgesic drugs.
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Antinociceptive and anti-inflammatory potential of extract and isolated compounds from the leaves of Salvia officinalis in mice.
J Ethnopharmacol
PUBLISHED: 09-06-2011
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Salvia officinalis L. has been used as a traditional herbal medicine for gastric disturbances and inflammatory processes. This study investigated the toxicological, antinociceptive and anti-inflammatory effects of the hydroalcoholic extract (HE) from leaves of Salvia officinalis and its isolated compounds in mice.
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A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing.
Blood
PUBLISHED: 08-25-2011
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Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe GVHD is usually absent. However, little is known regarding optimal T-cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2-step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after CY. A dose of 2 × 10(8)/kg of T cells resulted in consistent engraftment, immune reconstitution, and acceptable rates of GVHD. Cumulative incidences of grade III-IV GVHD, nonrelapse mortality (NRM), and relapse-related mortality were 7.4%, 22.2%, and 29.6%, respectively. With a follow-up of 28-56 months, the 3-year probability of overall survival for the whole cohort is 48% and 75% in patients without disease at HSCT. In the context of CY tolerization, a high, fixed dose of haploidentical T cells was associated with encouraging outcomes, especially in good-risk patients, and can serve as the basis for further exploration and optimization of this 2-step approach. This study is registered at www.clinicaltrials.gov as NCT00429143.
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Influence of a peracetic acid-based immersion on indirect composite resin.
Eur J Prosthodont Restor Dent
PUBLISHED: 07-26-2011
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The aim of this study was to evaluate the influence of immersion in a 0.2% peracetic acid-based disinfectant on the three-point flexural strength, water sorption and water solubility of an indirect composite resin. Specimens were produced according to ISO 4049:2000 specifications and were divided in two groups: Control group, with no disinfection and Disinfected group, with three 10 min immersions in the peracetic acid intercalated with 10 min immersions in sterile distilled water. All evaluations were conducted in compliance with ISO specifications. Three-point flexural strength, water sorption and solubility of indirect composite resin before and after immersion showed no statistical significant differences (p > 0.05) and met ISO standard requirements. Immersion in peracetic acid solution showed no influence in indirect composite resin tested properties.
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Isolation of a gastroprotective arabinoxylan from sugarcane bagasse.
Bioresour. Technol.
PUBLISHED: 07-05-2011
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After industrial processing, one-third of sugarcane culms is converted into residual bagasse. The xylan-rich hemicellulose components of the bagasse were extracted with hot aqueous alkali (AX-CRUDE). Approximately 82% of the extracted hemicelluloses was precipitated with ethanol (AX-PET). Both AX-CRUDE and AX-PET contained an arabinoxylan as confirmed by 13C NMR and methylation analysis. Fraction AX-PET was fed to female Wistar rats with ethanol-induced gastric lesions. Oral administrations of 30, 100, and 300 mg/kg reduced the gastric lesion area by over 50%, and replenished ethanol-induced depletion of glutathione. The polysaccharide also increased mucus production by over 70%, indicating its cytoprotective action on experimentally induced gastric ulcers. These findings are significant, since a biologically active compound can be extracted in high yields from an abundant, readily available residue.
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Determination of internal target volume using selective phases of a 4-dimensional computed tomography scan.
Pract Radiat Oncol
PUBLISHED: 06-24-2011
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Internal target volume (ITV) is frequently determined by contouring of gross tumor volumes (GTV) on 10 phases of a 4-dimensional computed tomography (4DCT) study set for lung cancer radiotherapy. This study aimed to investigate the possibility of generating ITV by using selective phases of a 4DCT scan.
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Improving prognosis of glioblastoma in the 21st century: who has benefited most?
Cancer
PUBLISHED: 06-21-2011
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Glioblastoma multiforme (GBM) is the most frequent primary brain tumor in adults. Temozolomide was rapidly incorporated into first-line treatment following the publication of the pivotal European Organization for Research and Treatment of Cancer-National Cancer Institute of Canada phase 3 trial in 2005. However, in the trial, enrollment was limited to younger patients with good performance status. Therefore, this study performed a population-based survival analysis of patients with newly diagnosed GBM covering the period before and after the introduction of temozolomide.
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Impact of the implantation of a new curriculum in the process of learning in a Faculty of Dentistry in Brazil.
Braz Oral Res
PUBLISHED: 06-16-2011
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The aim of the present study was to evaluate two dental curricula at a school of dentistry in southern Brazil. The study population included dentists trained in the last two classes of the institutions old curriculum (n = 98) and graduates of the first two classes of the new curriculum (n = 56). A questionnaire with open and closed questions was used for an overall evaluation of different aspects of the curricula, such as study methods, importance given to basic sciences, quality of theoretical and clinical guidance, perception about skills needed to perform different dental procedures, professional goals and an overall assessment. Students in the new curriculum reported more frequent use of the internet (69.6%) and scientific articles (50.0%). More importance was given to the basic sciences in the new curriculum. Graduates of the old curriculum alleged themselves to be more capable of both performing conventional (99%) and complex amalgam restorations (68.4%), as well as three-unit fixed prostheses (62.2%). Graduates of the new curriculum alleged higher capability with periodontal surgeries (48.2%), treatment of temporomandibular joint (TMJ) disorders (58.1%) and public health planning (78.6%). Regarding professional goals, the new curriculum was associated with an increase in the graduates willingness to work in the public health system and to pursue an academic career. New curriculum graduates reported higher overall assessments regarding their educational, as well as theoretical and clinical, outcomes. A new curricular approach was associated with several changes from the perspective of the students.
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Involvement of Interleukin-10 in the Anti-Inflammatory Effect of Sanyinjiao (SP6) Acupuncture in a Mouse Model of Peritonitis.
Evid Based Complement Alternat Med
PUBLISHED: 06-05-2011
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In this study, we determined the anti-inflammatory effect of manual acupuncture at the Sanyinjiao or Spleen 6 (SP6) point on carrageenan-induced peritonitis in mice and investigated mechanisms that may underlie this effect. In the first set of experiments, male Swiss mice were allocated into five groups: the control (sterile saline), dexamethasone (DEXA), invasive sham-acupuncture (non-acupoint), SP6 acupuncture and carrageenan-treated groups. Ten minutes after needle retention or 30?min after DEXA treatment, mice received an intraperitoneal injection of carrageenan (750??g/mouse). After 4?h, total leukocyte and differential cell counts (neutrophils and mononuclear), myeloperoxidase (MPO) activity, vascular permeability and cytokine levels were evaluated. In another set of experiments, adrenalectomized (ADX) mice were used to study the involvement of the adrenal gland on the therapeutic effects of acupuncture. Mice were allocated into two groups: the ADX and sham-operated animals (Sham ADX) that were subdivided into four subgroups each: the control (sterile saline), DEXA, SP6 acupuncture and carrageenan-treated groups. The SP6 and DEXA treatments inhibited the inflammatory cell infiltration, vascular permeability and MPO activity in carrageenan-injected mice. In addition, the SP6 treatment also increased interleukin (IL)-10 levels. In contrast, when the animals were adrenalectomized, the SP6 treatment failed to reduce total leukocyte and the plasma extravasation. In conclusion, this study clearly demonstrates the anti-inflammatory effect of SP6 acupuncture in a model of carrageenan-induced peritonitis. Our results demonstrated that SP6 acupuncture depends of the adrenal glands and increased IL-10 levels to produce its anti-inflammatory action.
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Influence of 2-hydroxyethyl methacrylate concentration on polymer network of adhesive resin.
J Adhes Dent
PUBLISHED: 05-20-2011
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To evaluate the effect of variations in 2-hydroxyethyl methacrylate (HEMA) concentrations in an experimental comonomer blend on degree of conversion, water sorption, solubility, and ultimate tensile strength of adhesive resin.
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Multiple courses of stereotactic re-irradiation in recurrent oligodendroglioma: a case report.
J Med Case Rep
PUBLISHED: 05-14-2011
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High grade gliomas are an insidious disease associated with an extremely poor prognosis. The role of re-irradiation for recurrent gliomas is unclear but several retrospective studies have indicated mild toxicity and modest outcomes with this regimen. With subsequent progression, it is unclear what options remain and more radiotherapy is rarely offered for fear of surpassing normal central nervous system tissue tolerance and causing significant side effects without significant benefit.
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Phase II study of cetuximab in combination with chemoradiation in patients with stage IIIA/B non-small-cell lung cancer: RTOG 0324.
J. Clin. Oncol.
PUBLISHED: 05-09-2011
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Non-small-cell lung cancer (NSCLC) commonly expresses the epidermal growth factor receptor (EGFR), which is associated with poor clinical outcome. Cetuximab is a chimerized monoclonal antibody that targets the EGFR and, in preclinical models, it demonstrates radiosensitization properties. We report a phase II trial testing the combination of cetuximab with chemoradiotherapy (CRT) in unresectable stage III NSCLC.
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What is the best way to contour lung tumors on PET scans? Multiobserver validation of a gradient-based method using a NSCLC digital PET phantom.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 04-29-2011
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To evaluate the accuracy and consistency of a gradient-based positron emission tomography (PET) segmentation method, GRADIENT, compared with manual (MANUAL) and constant threshold (THRESHOLD) methods.
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Safety and feasibility of motexafin gadolinium administration with whole brain radiation therapy and stereotactic radiosurgery boost in the treatment of ? 6 brain metastases: a multi-institutional phase II trial.
J. Neurooncol.
PUBLISHED: 04-18-2011
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To determine the safety, tolerability, and report on secondary efficacy endpoints of motexafin gadolinium (MGd) in combination with whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) for patients with ? 6 brain metastases. We conducted an international study of WBRT (37.5 Gy in 15 fractions) and SRS (15-21 Gy) with the addition of MGd (5 mg/kg preceding each fraction beginning week 2). The primary endpoint was to evaluate the rate of irreversible grade 3 or any grade ? 4 neurotoxicity and establish feasibility in preparation for a phase III trial. Sixty-five patients were enrolled from 14 institutions, of which 45 (69%) received SRS with MGd as intended and were available for evaluation. Grade ? 3 neurotoxicity attributable to radiation therapy within 3 months of SRS was seen in 2 patients (4.4%), including generalized weakness and radionecrosis requiring surgical management. Immediately following the course of MGd plus WBRT, new brain metastases were detected in 11 patients (24.4%) at the time of the SRS treatment planning MRI. The actuarial incidence of neurologic progression at 6 months and 1 year was 17 and 20%, respectively. The median investigator-determined neurologic progression free survival and overall survival times were 8 (95% CI: 5-14) and 9 months (95% CI: 6-not reached), respectively. We observed a low rate of neurotoxicity, demonstrating that the addition of MGd does not increase the incidence or severity of neurologic complications from WBRT with SRS boost.
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Influence of chlorhexidine application on longitudinal adhesive bond strength in deciduous teeth.
Braz Oral Res
PUBLISHED: 03-29-2011
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The aim of this study was to evaluate the influence of applying 2% chlorhexidine for 30 seconds after phosphoric acid conditioning of dentin on the immediate and long-term bond strengths in deciduous teeth. The occlusal enamel was removed from 40 human sound deciduous molars, which were exfoliated by natural means, and the dentin was conditioned with 37% phosphoric acid for 15 seconds and washed with running water. The specimens were divided into two groups of 20 teeth. The test group received an application of 2% chlorhexidine for 30 seconds prior to a three-step etch-and-rinse adhesive system, whereas the control group received only the adhesive system. Three cylindrical restorations were made with a composite resin for each tooth. Ten teeth in each group were submitted to a microshear bond strength test after 24 hours, while the remaining teeth were stored in distilled water at 37 °C for 6 months before testing the microshear bond strength. The test group had a higher bond strength than did the control group after 6 months of storage. No statistical differences were found when groups with the same dentin treatment were compared at different times. Short applications of chlorhexidine at low concentrations prevent hybrid layer degradation and positively affect bond strength over time.
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Phase i study of dose-dense pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma.
Radiat Oncol
PUBLISHED: 02-16-2011
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This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC).
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2-O-ribose methylation of cap2 in human: function and evolution in a horizontally mobile family.
Nucleic Acids Res.
PUBLISHED: 02-09-2011
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The 5 cap of human messenger RNA consists of an inverted 7-methylguanosine linked to the first transcribed nucleotide by a unique 5-5 triphosphate bond followed by 2-O-ribose methylation of the first and often the second transcribed nucleotides, likely serving to modify efficiency of transcript processing, translation and stability. We report the validation of a human enzyme that methylates the ribose of the second transcribed nucleotide encoded by FTSJD1, henceforth renamed HMTR2 to reflect function. Purified recombinant hMTr2 protein transfers a methyl group from S-adenosylmethionine to the 2-O-ribose of the second nucleotide of messenger RNA and small nuclear RNA. Neither N(7) methylation of the guanosine cap nor 2-O-ribose methylation of the first transcribed nucleotide are required for hMTr2, but the presence of cap1 methylation increases hMTr2 activity. The hMTr2 protein is distributed throughout the nucleus and cytosol, in contrast to the nuclear hMTr1. The details of how and why specific transcripts undergo modification with these ribose methylations remains to be elucidated. The 2-O-ribose RNA cap methyltransferases are present in varying combinations in most eukaryotic and many viral genomes. With the capping enzymes in hand their biological purpose can be ascertained.
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Acute esophagitis and late lung toxicity in concurrent chemoradiotherapy trials in patients with locally advanced non-small-cell lung cancer: analysis of the radiation therapy oncology group (RTOG) database.
Clin Lung Cancer
PUBLISHED: 01-28-2011
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We analyzed time course and factors associated with acute esophagitis (ES) and late lung toxicity (PN), as well as any association between ES and PN in patients (pts) with non-small-cell lung cancer (NSCLC) treated with concurrent chemoradiation (chemo-RT) on the Radiation Therapy Oncology Group (RTOG) trials.
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A phase 1b trial of the combination of the antiangiogenic agent sunitinib and radiation therapy for patients with primary and metastatic central nervous system malignancies.
Cancer
PUBLISHED: 01-19-2011
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In this phase 1 trial, the authors evaluated sunitinib combined with radiation therapy (RT) for the treatment of primary or metastatic central nervous system (CNS) malignancies.
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Further antinociceptive effects of myricitrin in chemical models of overt nociception in mice.
Neurosci. Lett.
PUBLISHED: 01-19-2011
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The present work explored the antinociceptive effects of the flavonoid myricitrin in models of overt nociception triggered by intraplantar injection of chemical algogens into the hind paw of mice. The nociception induced by bradykinin (3 nmol/paw i.pl.) was abolished by prior treatment with myricitrin (10-100mg/kg, i.p.) with ID(50) of 12.4 (8.5-18.1)mg/kg. In sharp contrast, myricitrin failed to affect the nociception elicited by prostaglandin E(2) (3 nmol/paw i.pl.). Cinnamaldehyde (10 nmol/paw i.pl.)-induced nociception was reduced by myricitrin (100mg/kg, i.p.) and camphor (7.6 mg/kg,s.c.) in 43±10% and 57±8%, respectively. Myricitrin (30-100mg/kg, i.p.) and amiloride (100mg/kg, i.p.) inhibited nociceptive responses induced by acidified saline (pH 5/paw i.pl.), with ID(50) of 22.0 (16.1-30.0)mg/kg and inhibition of 71±6% and 64±5%, respectively. Moreover, myricitrin (10-30 mg/kg, i.p.) and ruthenium red (3mg/kg, i.p.) significantly reduced the nociception induced by menthol (1.2 ?mol/paw i.pl.) with the mean ID(50) of 2.4 (1.5-3.7)mg/kg and inhibition of 95±3% and 51±7%, respectively. In addition, myricitrin administration (30 and 100mg/kg, i.p.) markedly reduced menthol-induced mechanical allodynia. However, myricitrin (100mg/kg, i.p.) prevented (only in time of 60 min) cold allodynia induced by menthol. Collectively, the present results extend prior data and show that myricitrin promotes potent antinociception, an action that is likely mediated by an inhibition of the activation of nociceptors by bradykinin and TRPs agonist (i.e. cinnamaldehyde, acidified saline and menthol), probably via inhibition of PKC pathways. Thus, myricitrin could constitute an attractive molecule of interest for the development of new analgesic drugs.
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Antimicrobial activity of [2-(methacryloyloxy)ethyl]trimethylammonium chloride against Candida spp.
Rev Iberoam Micol
PUBLISHED: 01-14-2011
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Candida-associated denture stomatitis is the most common manifestation of oral candidal infection, caused mainly by Candida albicans. Several authors have attempted to add antifungal agents or antiseptics to denture temporary soft lining materials or to denture acrylic resins, without relevant results. Therefore, the investigation of a quaternary ammonium functionalized compound [2-(methacryloyloxy)ethyl]trimethylammonium chloride (MADQUAT), which copolymerizes with methacrylates and which could act as a fungal inhibitor, is of paramount importance.
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Phase III trial of prophylactic cranial irradiation compared with observation in patients with locally advanced non-small-cell lung cancer: neurocognitive and quality-of-life analysis.
J. Clin. Oncol.
PUBLISHED: 12-06-2010
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There are scant data regarding the effects of prophylactic cranial irradiation (PCI) on neurocognitive function (NCF) and quality of life (QOL). Radiation Therapy Oncology Group trial 0214 showed no overall survival (OS) benefit for PCI in stage III non-small-cell lung cancer (NSCLC) at 1 year. However, there was a significant decrease in brain metastases (BM). This analysis focuses on the impact of PCI on NCF and QOL.
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The American Society for Radiation Oncologys 2010 core physics curriculum for radiation oncology residents.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 05-28-2010
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In 2004, the American Society for Radiation Oncology (ASTRO) published its first physics education curriculum for residents, which was updated in 2007. A committee composed of physicists and physicians from various residency program teaching institutions was reconvened again to update the curriculum in 2009.
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Hypofractionated stereotactic radiation therapy: an effective therapy for recurrent high-grade gliomas.
J. Clin. Oncol.
PUBLISHED: 05-17-2010
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Salvage options for recurrent high-grade gliomas (HGGs) are limited by cumulative toxicity and limited efficacy despite advances in chemotherapeutic and radiotherapeutic techniques. Previous studies have reported encouraging survival results and favorable toxicity with fractionated stereotactic radiotherapy, and small studies have shown similar benefit using a shortened course of hypofractionated stereotactic radiation therapy (H-SRT). We sought to determine the efficacy and toxicity profile of H-SRT alone or in addition to repeat craniotomy or concomitant chemotherapy.
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Antiulcerogenic activity of hydroalcoholic extract of Achillea millefolium L.: involvement of the antioxidant system.
J Ethnopharmacol
PUBLISHED: 03-29-2010
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Achillea millefolium L. is a member of the Asteraceae family that is commonly referred to as "yarrow" and has been used in folk medicine against several disturbances including skin inflammations, spasmodic and gastrointestinal disorders, as well as hepato-biliary complaints.
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Primary analysis of a phase II randomized trial Radiation Therapy Oncology Group (RTOG) 0212: impact of different total doses and schedules of prophylactic cranial irradiation on chronic neurotoxicity and quality of life for patients with limited-disease
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 03-23-2010
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To determine the effect of dose and fractionation schedule of prophylactic cranial irradiation (PCI) on the incidence of chronic neurotoxicity (CNt) and changes in quality of life for selected patients with limited-disease small-cell lung cancer (LD SCLC).
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Preclinical challenges in steroid analysis of human samples.
J. Steroid Biochem. Mol. Biol.
PUBLISHED: 03-02-2010
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Preclinical challenges in the analysis of steroid hormones are primarily determined by biological factors involved in the physiology and pathophysiology of hormone secretion. Major biologically influencing factors like age, sex, pubertal stage, pregnancy, phase of the menstruation, and diurnal rhythm have to be considered in the definition of reference ranges for steroids and their clinical interpretation. Hitherto, in clinical routine laboratories steroids were mainly determined by direct immunoassays applied on automated platforms, which are simple, rapid and cheap if a high number of samples are measured. However, technical factors like cross-reactivity of related steroid metabolites or limited analytical ranges have to be taken in account and may impair accuracy and precision of these direct methods. The actual development of mass spectrometry based analytical platforms for the determination of single steroid or steroid patterns seems to be an alternative analytical approach combining multi-parametric analysis, high sensitivity and specificity as well simple sample pre-treatment, robustness and low running costs for steroid analysis. This short review will give an overview about biological influencing factors and technical disturbing factors of routinely used immunoassay for the analysis of steroids. The application of LC-MS/MS as an alternative routine high-throughput platform for steroid analysis and its perspective role in the standardization and harmonisation of steroid measurements in clinical routine application will be discussed.
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Influence of chlorhexidine application at longitudinal push-out bond strength of fiber posts.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod
PUBLISHED: 02-24-2010
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The objective of this study was to evaluate the influence of chlorhexidine application after dentin phosphoric acid etching at immediate and long-term bond strength of a fiber post cemented to root dentin.
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Radiation dose-volume effects in the esophagus.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-23-2010
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Publications relating esophageal radiation toxicity to clinical variables and to quantitative dose and dose-volume measures derived from three-dimensional conformal radiotherapy for non-small-cell lung cancer are reviewed. A variety of clinical and dosimetric parameters have been associated with acute and late toxicity. Suggestions for future studies are presented.
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Lipodystrophy syndrome and cardiovascular risk factors in children and adolescents infected with HIV/AIDS receiving highly active antiretroviral therapy.
J Pediatr (Rio J)
PUBLISHED: 02-13-2010
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To describe lipid profile, body shape changes, and cardiovascular risk factors in children and adolescents infected with HIV/AIDS receiving highly active antiretroviral therapy.
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The antinociceptive effect of (-)-linalool in models of chronic inflammatory and neuropathic hypersensitivity in mice.
J Pain
PUBLISHED: 02-11-2010
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We used multiple pain models to investigate the effects of (-)-linalool, a monoterpene alcohol present in the essential oil of plants, on chronic inflammatory and neuropathic hypersensitivity in adult Swiss mice. Inflammatory or neuropathic hypersensitivity was induced by intraplantar (i.pl.) injection of complete Freunds adjuvant (CFA) or partial sciatic nerve ligation (PSNL), respectively. Twenty-four hours after CFA injection, we used Von Frey filaments and acetone-evoked cooling to evaluate tactile and thermal hypersensitivity, respectively. A single i.p. injection of (-)-linalool (50 or 200 mg/kg) administered 30 minutes before testing reduced CFA-induced mechanical hypersensitivity. Similarly, (-)-linalool reduced acetone-evoked hypersensitivity up to 4 hours after treatment. Compared with vehicle, (-)-linalool produced a marked reduction in CFA-induced paw edema. (-)-Linalool also reduced mechanical hypersensitivity induced by PSNL 7 days after injury. Multiple (-)-linalool treatments given chronically (twice a day for 10 days; 50 mg/kg, i.p.) significantly reduced mechanical hypersensitivity induced by CFA and PSNL. This multidose strategy did not cause tolerance. We also reasoned that (-)-linalool might reduce nociceptive behavior in response to direct administration of inflammatory mediators. Therefore, we injected the cytokines IL-1? (.1 pg/site) and TNF-? (1 pg/site) intrathecally. (-)-Linalool inhibited the biting response induced by IL-1? and TNF-?.
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Contribution of peripheral endothelin ETA and ETB receptors in neuropathic pain induced by spinal nerve ligation in rats.
Eur J Pain
PUBLISHED: 02-10-2010
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Endothelins (ETs) contribute to the sensory changes seen in animals models of inflammatory, cancer and diabetic neuropathic pain, but little is known about their nociceptive role following peripheral nerve injury. The current study evaluated mechanisms by which ETs can drive changes in nociceptive responses to thermal stimulation of the hind paw of rats induced by unilateral lumbar L5/L6 spinal nerve ligation (SNL) injury. SNL sensitizes rats to acetone-evoked cooling of and radiant heat application (Hargreaves test) to the ipsilateral hind paw (throughout 3-40 and 9-40 days after surgery, respectively). At 12 days after SNL, intraplantar (i.pl.) injection of endothelin-1 (ET-1, 10 pmol) induces greater overt nociception that was reduced only by treatment with the selective ET(A) peptidic antagonist (BQ-123, 10 nmol, i.pl), but unchanged by the selective ET(B) peptidic antagonist (BQ-788). Cold allodynia evoked by cooling the ipsilateral hind paw with acetone was reduced by i.pl. injection of both antagonists BQ-123 or BQ-788 (3 or 10 nmol). In contrast, heat hyperalgesia evaluated by Hargreaves method was reduced only by BQ-123. SNL enhanced the [Ca(+2)](i) increases induced by ET-1 (100 nM) in neurons from L5/L6 (injured) and L4 (intact) cultured dorsal root ganglion, but did not change the responses of non-neuronal cells. Furthermore, Western blot analysis revealed that SNL increased ET(A) and ET(B) receptor protein expression in spinal nerves. Thus, SNL induces marked hind paw hypersensitivity to thermal stimulation in part via up-regulation of peripheral sensory nerve pronociceptive ET(A) and ET(B) receptor-operated mechanisms.
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FR-like EBNA1 binding repeats in the human genome.
Virology
PUBLISHED: 01-28-2010
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Epstein-Barr virus (EBV) is widely spread in the human population. EBV nuclear antigen 1 (EBNA1) is a transcription factor that activates viral genes and is necessary for viral replication and partitioning, which binds the EBV genome cooperatively. We identify similar EBNA1 repeat binding sites in the human genome using a nearest-neighbor positional weight matrix. Previously experimentally verified EBNA1 sites in the human genome are successfully recovered by our approach. Most importantly, 40 novel regions are identified in the human genome, constituted of tandemly repeated binding sites for EBNA1. Genes located in the vicinity of these regions are presented as possible targets for EBNA1-mediated regulation. Among these, four are discussed in more detail: IQCB1, IMPG1, IRF2BP2 and TPO. Incorporating the cooperative actions of EBNA1 is essential when identifying regulatory regions in the human genome and we believe the findings presented here are highly valuable for the understanding of EBV-induced phenotypic changes.
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Reirradiation human spinal cord tolerance for stereotactic body radiotherapy.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 01-26-2010
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We reviewed the treatment for patients with spine metastases who initially received conventional external beam radiation (EBRT) and were reirradiated with 1-5 fractions of stereotactic body radiotherapy (SBRT) who did or did not subsequently develop radiation myelopathy (RM).
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Quality of life supersedes the classic prognosticators for long-term survival in locally advanced non-small-cell lung cancer: an analysis of RTOG 9801.
J. Clin. Oncol.
PUBLISHED: 10-26-2009
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To determine the added value of quality of life (QOL) as a prognostic factor for overall survival (OS) in patients with locally advanced non-small-cell lung cancer (NSCLC) treated on Radiation Therapy Oncology Group RTOG-9801.
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A computational study of lambda-lac mutants.
Phys Biol
PUBLISHED: 10-08-2009
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We present a comprehensive, computational study of the properties of bacteriophage lambda mutants designed by Atsumi and Little (2006 Proc. Natl. Acad. Sci. 103 4558-63). These phages underwent a genetic reconstruction where Cro was replaced by a dimeric form of the Lac repressor. To clarify the theoretical characteristics of these mutants, we built a detailed thermodynamic model. The mutants all have a different genetic wiring than the wild-type lambda. One group lacks regulation of P(RM) by the lytic protein. These mutants only exhibit the lysogenic equilibrium, with no transiently active P(R). The other group lacks the negative feedback from CI. In this group, we identify a handful of bi-stable mutants, although the majority only exhibit the lysogenic equilibrium. The experimental identification of functional phages differs from our predictions. From a theoretical perspective, there is no reason why only 4 out of 900 mutants should be functional. The differences between theory and experiment can be explained in two ways. Either, the view of the lambda phage as a bi-stable system needs to be revised, or the mutants have in fact not undergone a modular replacement, as intended by Atsumi and Little, but constitute instead a wider systemic change.
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High-dose-rate surface brachytherapy to boost elongated, curvilinear incisional scars after extrapleural pneumonectomy for malignant pleural mesothelioma treated with adjuvant intensity-modulated radiation therapy.
Brachytherapy
PUBLISHED: 07-10-2009
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Providing adequate dosimetric coverage of elongated, curvilinear incisions during adjuvant intensity-modulated radiation therapy (IMRT) after extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) creates technical challenges. We explored high-dose-rate (HDR) surface brachytherapy to supplement dose to multiple curvilinear incisions. This modality circumvents the technical limitations of relying on multiple en face electron fields while minimizing dose to adjacent normal tissues.
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Shear bond strength of metallic brackets: influence of saliva contamination.
J Appl Oral Sci
PUBLISHED: 05-26-2009
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To evaluate the influence of saliva contamination on shear bond strength and the bond failure pattern of 3 adhesive systems (Transbond XT, AdheSE and Xeno III) on orthodontic metallic brackets bonded to human enamel.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.