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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
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Widder Randolf A. Lappas Alexandra Rennings Corinna Hild Matthias Roessler Gernot F. Dietlein Thomas S. 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2020,258(11):2581-2581
Graefe's Archive for Clinical and Experimental Ophthalmology - The published online version contains mistake as the author's first name and last name have been interchanged as "Hild... 相似文献
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Alexandra B. Morshed Rachel G. Tabak Cynthia D. Schwarz Debra Haire-Joshu 《Journal of nutrition education and behavior》2019,51(2):237-244
Objective
To examine whether a healthy weight intervention embedded in the Parents as Teachers (PAT) home visiting program, which was previously found to improve mothers’ body mass index (BMI) and obesity-related behaviors, changed the BMI of preschool children or maternal feeding practices.Methods
This stratified randomized trial included preschool-aged children at risk for overweight whose mothers were overweight or had obesity (n?=?179). The Healthy Eating and Active Living Taught at Home (HEALTH) intervention was based on the Diabetes Prevention Program. Differences were examined using repeated-measures mixed-ANOVA models.Results
Compared with PAT usual care, the HEALTH intervention had no effect on children's BMI or maternal feeding practices. However, combined analyses showed that children's BMI percentile decreased (P??=?.007), BMI z-scores were maintained (P??=?.19), and 3 of 8 feeding practices improved over time (P < .05).Conclusions and Implications
Additional research is needed to assess the effectiveness of PAT to prevent preschool-age obesity using rigorous designs (eg, group-randomized trials) and to identify its active components. HEALTH is ready to be scaled up to prevent maternal weight gain through embedding within the national PAT program. 相似文献5.
Seyed Mehdi BagheriMofidi Majid Pouladian Seyed Behnamedin Jameie Ali Abbaspour Tehrani-Fard 《Australasian physical & engineering sciences in medicine / supported by the Australasian College of Physical Scientists in Medicine and the Australasian Association of Physical Sciences in Medicine》2016,39(3):717-726
Magnetic field generated by neuronal activity could alter magnetic resonance imaging (MRI) signals but detection of such signal is under debate. Previous researches proposed that magnitude signal change is below current detectable level, but phase signal change (PSC) may be measurable with current MRI systems. Optimal imaging parameters like echo time, voxel size and external field direction, could increase the probability of detection of this small signal change. We simulate a voxel of cortical column to determine effect of such parameters on PSC signal. We extended a laminar network model for somatosensory cortex to find neuronal current in each segment of pyramidal neurons (PN). 60,000 PNs of simulated network were positioned randomly in a voxel. Biot–savart law applied to calculate neuronal magnetic field and additional phase. The procedure repeated for eleven neuronal arrangements in the voxel. PSC signal variation with the echo time and voxel size was assessed. The simulated results show that PSC signal increases with echo time, especially 100/80 ms after stimulus for gradient echo/spin echo sequence. It can be up to 0.1 mrad for echo time = 175 ms and voxel size = 1.48 × 1.48 × 2.18 mm3. With echo time less than 25 ms after stimulus, it was just acquired effects of physiological noise on PSC signal. The absolute value of the signal increased with decrease of voxel size, but its components had complex variation. External field orthogonal to local surface of cortex maximizes the signal. Expected PSC signal for tactile detection in the somatosensory cortex increase with echo time and have no oscillation. 相似文献
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Alexandra Elliott Laura Schoenlaub Danielle Freches William Mitchell Guoquan Zhang 《Infection and immunity》2015,83(8):3104-3113
Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes the zoonotic disease Q fever. Although Q fever is mainly transmitted by aerosol infection, study of the immune responses in the lung following pulmonary C. burnetii infection is lacking. Neutrophils are considered the first immune cell to migrate into the lung and play an important role in host defense against aerosol infection with microbial pathogens. However, the role of neutrophils in the host defense against C. burnetii infection remains unclear. To determine the role of neutrophils in protective immunity against C. burnetii infection, the RB6-8C5 antibody was used to deplete neutrophils in mice before intranasal infection with C. burnetii. The results indicated that neutrophil-depleted mice developed more severe disease than their wild-type counterparts, suggesting that neutrophils play an important role in host defense against C. burnetii pulmonary infection. We also found that neither CXC chemokine receptor 2 (CXCR2) nor interleukin-17 (IL-17) receptor (IL-17R) deficiency changed the severity of disease following intranasal C. burnetii challenge, suggesting that keratinocyte-derived chemokine and IL-17 may not play essential roles in the response to C. burnetii infection. However, significantly higher C. burnetii genome copy numbers were detected in the lungs of IL-1R−/− mice at 14 days postinfection. This indicates that IL-1 may be important for the clearance of C. burnetii from the lungs following intranasal infection. Our results also suggest that neutrophils are involved in protecting vaccinated mice from C. burnetii challenge-induced disease. This is the first study to demonstrate an important role for neutrophils in protective immunity against C. burnetii infection. 相似文献
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Improvement in Tricuspid Annular Plane Systolic Excursion with Pulmonary Hypertension Therapy in Pediatric Patients 下载免费PDF全文
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