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1.
Emeline Colomba Patricia Pautier Fanny Pommeret Alexandra Leary 《Expert review of anticancer therapy》2019,19(6):437-446
Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.
Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.
Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited. 相似文献
2.
Hsiu Hui Chiu Hsiao Hui Chou Wen Dar Jean Wung Yang Shieh 《Journal of microbiology, immunology, and infection》2007,40(1):14-23
BACKGROUND AND PURPOSE: Marine luminous bacteria were isolated and identified from samples in shallow coastal waters of Taiwan during the relatively warm seasons. METHODS: Identification of the luminous isolates was performed based on differences of phenotypic and genotypic characteristics together with data from phylogenetic analysis. RESULTS: Twenty seven strains of marine luminous bacteria were isolated. They were divided into five types based on differences of phenotypic characteristics. However, they could be clustered into only two genotypes according to the analysis of restriction patterns of polymerase chain reaction-amplified 16S rRNA genes digested with various restriction enzymes. The characterization data together with the 16S rRNA gene-based phylogenetic analysis revealed that the isolates included in phenotype I (seven isolates) could be Photobacterium leiognathi, and those included in phenotypes II-V (twenty isolates) might be classified as Vibrio harveyi. However, phylogeny based on gyrB sequences indicated that phenotypes II-V could be classified into two species, V. harveyi and Vibrio campbellii. CONCLUSION: Culturable luminous bacteria in the shallow coastal waters of Taiwan during the sampling period are dominated by V. harveyi/campbellii and P. leiognathi, and the former species appeared to be more prevalent and numerous than the latter species in general. 相似文献
3.
S. Kumar N. H. Dar M. Ashraf S. C. Sharma V. Maheshwari 《Indian journal of otolaryngology and head and neck surgery》2004,56(1):37-39
We report a cast of ossifying fibroma of the nose, arising from the bony septum and extending into the nasophaynx in a 2 yrs.
old child presenting with features of obstructed nose. 相似文献
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Steroids are usually identified as genomic regulators, yet recently a body of evidence has accumulated demonstrating specific plasma membrane effects, as well as coordinative effects, of some steroids on both membrane and intracellular receptors. The resulting rapid (<1 min) modulation of cellular activity has strongly suggested a non-genomic, and possibly modulatory, role for certain steroid compounds, and dramatic effects on membranes of excitable as well as other tissues have been demonstrated. Steroid synthesis and metabolism have been shown to exist in the CNS, and the effects have been seen in both the central and peripheral nervous systems. The major groups of neuroactive steroids, and their metabolites, have been progesterone, deoxycorticosterone, and some androgens, notably dihydroxyepiandrosterone (DHEA). These compounds show increased concentrations both in blood and in the brain following stress and they have also been associated with anxiolytic effects and antiepileptic activity. In the periphery, some of these compounds show remarkable inhibitory effects on the secretion of catecholamines and other neurotransmitters. The mechanism for the majority of the effects of these steroids is via their effect on receptor-mediated binding to ligand-gated ion channels. Activation of the GABAA receptor complex, resulting in the opening of its central chloride channel, is the major target of the neuroactive steroids, resulting in re-polarization of the plasma membrane and inhibition of further neuronal firing. The anxiolytic, anti-convulsant and sedative-hypnotic actions of these neuroactive steroids have resulted in their being used as therapeutic agents for the treatment of anxiety, epilepsy, insomnia, and possibly for the alteration of pain thresholds. 相似文献
7.
Federico Ferrando-Castagnetto Enrique Macri Alejandro Silva Darío Padula Gastón Garcés 《Educación Médica》2019
Introduction
Although an objective structured clinical examination (OSCE) format has been applied in Uruguay since 2004, and providing reliable performance measures, perceptions of it properties and level of student satisfaction have not been determined.Objective
To evaluate the face validity of OSCE format as a contribution to its local feasibility study.Material and methods
At the end of the introductory clinical course, the sub-cohort enrolled at the University Hospital responded to a 28-item questionnaire aimed at exploring perceptions about the properties of the OSCE about the potential factors ‘design’ and ‘apparent validity’. After analysing the reliability of the original questionnaire, the questionnaire was refined in an attempt to provide a shorter and more reliable tool.Results
The original questionnaire showed good internal consistency (Cronbach alpha = 0.70), with a dominance of ‘agreement/total agreement’ opinions on authenticity of the stimuli, dynamic, relevance, and equity of the test. Students perceived organisational obstacles during the test, expressing disagreement to include some stations only aimed at assessing communication skills, and requiring personalised feedback sessions. The refined version of the questionnaire provides consistent measures on student perceptions and is a useful tool that can be widely applied. A discussion is presented on the contributions of this experience to a comprehensive feasibility study of the new format during curriculum transition.Conclusions
The OSCE is well evaluated by students at the end of the propaedeutic course, supporting its validity. Educational potentials of the new format should be exploited, providing effective feedback to students, clinical teachers, and institutions. 相似文献8.
Zvi Borochowitz Lorenzo Pavone Galia Mazor Renata Rizzo Hanna Dar 《American journal of medical genetics. Part A》1992,43(4):678-685
Five unrelated patients (a male and 4 females) were affected with a previously undefined multiple congenital anomalies/mental retardation syndrome which has been designated the facio-cutaneous-skeletal (FCS) syndrome and which includes mental retardation with specific sociable, humorous behavior, characteristic facial appearance, excessive generalized skin, postnatal growth failure, and skeletal involvement. Consanguinity was noted in 2 patients, thus autosomal recessive inheritance is suggested. © 1992 Wiley-Liss, Inc. 相似文献
9.
Ken Dewitte Marc Claeys Emeline Van Craenenbroeck Koen Monsieurs Hein Heidbuchel Vicky Hoymans Tibor Stoop 《Pathophysiology》2019,26(1):53-59
Aims
We explored the effect of remote ischaemic conditioning (RIC) on endothelial function and on circulating mediators.Methods and results
In 20 healthy male volunteers (mean age 31?±?10 years), flow-mediated dilation (FMD) was measured before and after 20?min of arm ischaemia, followed by reperfusion. Remote ischaemic conditioning (RIC) was performed by applying 3 cycles of 5?min of ischaemia of the leg at the onset of index arm ischaemia. Each volunteer underwent the IR-induced vascular injury protocol with and without RIC in a crossover study design.In the control group, IR significantly reduced FMD (5.9?±?2.9% before IR vs. 2.2?±?3.7% after IR; p?<?0.001). This effect was significantly attenuated by performing RIC (FMD of 5.5?±?3.1% before IR vs. 4.0?±?3.4% % after IR; p for interaction?=?0.01). Serum levels of SOD and ADMA increased significantly whereas MCP-1 and VEGF levels decreased significantly.Only changes in SOD levels were significantly related to the degree of RIC induced protection (r²?=?0.34; p?=?0.018).Conclusion
RIC has protective effects against endothelial IR injury. Our biomarker study suggests that anti-oxidative stress mediators, such as SOD, seem to be more involved in the pathogenesis of RIC-induced protection in humans than angiogenesis factors or chemo-attractant cytokines. 相似文献10.
Israel Shapiro Zvi Borochowitz Shimon Degani Hanna Dar Izu Ibschitz Mordechai Sharf 《American journal of medical genetics. Part A》1992,43(3):602-605
A diagnosis of the Neu-Laxova syndrome (NLS) was made by ultrasonography at 32 wks of gestation. Ultrasonographic examination showed intrauterine growth retardation (IUGR), Dandy-Walker anomaly, choroid plexus cysts, receding forehead and microcephaly, bilateral cataract without prominent eyes, scalp edema with no generalized edema, retrognathia, curved penis, and flexion deformities of limbs. The findings in this case are consistent with NLS; however, they did not fit any of Curry's [1982] groups. Massive swelling of hands and feet were among the main manifestations in classic NLS cases. In the case presented herein, edema was noted only in the scalp. This might shed further light on the question of variability vs. heterogeneity in the NLS. This case shows the existing possibility of an early diagnosis of NLS and adds Dandy-Walker anomaly and choroid plexus cysts as new findings to this syndrome. © 1992 Wiley-Liss, Inc. 相似文献