Introduction: Dysregulation of histone deacetylase (HDAC) activity is an epigenetic hallmark of multiple myeloma (MM), leading to aberrant gene expression and cellular signaling in myeloma cell growth, survival and resistance to therapy. Hyper-methylation at diagnosis is a frequent observation, which eventually may convert to hypo-methylation during advanced phases.
Areas covered: A literature search on ‘HDAC inhibitors’ and ‘multiple myeloma’ was carried out using PubMed and Google Scholar in the preparation of this overview on clinical efficacy and safety data.
Expert opinion: First-generation non-selective HDAC inhibitors have demonstrated minimal single-agent activity in refractory MM. Subsequently, combination therapy has proven an improvement in progression-free survival (PFS) but not response rates. The main concerns are associated with toxicities. Ongoing studies on new and more selective agents, i.e. Romidepsin or Ricolinostat, are promising in terms of better efficacy and less toxicity. 相似文献
BackgroundIn October 2011, the Advisory Committee on Immunization Practices (ACIP) issued updated recommendations that all pregnant women routinely receive a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine.ObjectivesWe characterized reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received Tdap after this updated recommendation (2011–2015) and compared the pattern of adverse events (AEs) with the period before the updated recommendation (2005–2010).MethodsWe searched the VAERS database for reports of AEs in pregnant women who received Tdap vaccine after the routine recommendation (11/01/2011–6/30/2015) and compared it to published data before the routine Tdap recommendation (01/01/2005–06/30/2010). We conducted clinical review of reports and available medical records. The clinical pattern of reports in the post-recommendation period was compared with the pattern before the routine Tdap recommendation.ResultsWe found 392 reports of Tdap vaccination after the routine recommendation. One neonatal death but no maternal deaths were reported. No maternal or neonatal deaths were reported before the recommendation. We observed an increase in proportion of reports for stillbirths (1.5–2.8%) and injection site reactions/arm pain (4.5–11.9%) after the recommendation compared to the period before the routine recommendation for Tdap during pregnancy. We noted a decrease in reports of spontaneous abortion (16.7–1%). After the 2011 Tdap recommendation, in most reports, vaccination (79%) occurred during the third trimester compared to 4% before the 2011 Tdap recommendation. Twenty-six reports of repeat Tdap were received in VAERS; 13 did not report an AE. One medical facility accounted for 27% of all submitted reports.ConclusionsNo new or unexpected vaccine AEs were noted among pregnant women who received Tdap after routine recommendations for maternal Tdap vaccination. Changes in reporting patterns would be expected, given the broader use of Tdap in pregnant women in the third trimester. 相似文献
Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5?mg/ml and 10?mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases. 相似文献
Development of the Practical Solutions for Pesticide Safety guide used participatory research strategies to identify and evaluate solutions that reduce pesticide exposures for workers and their families and to disseminate these solutions. Project principles were (1) workplace chemicals belong in the workplace, and (2) pesticide handlers and farm managers are experts, with direct knowledge of production practices. The project’s participatory methods were grounded in self-determination theory. Practical solutions were identified and evaluated based on five criteria: practicality, adaptability, health and safety, novelty, and regulatory compliance. Research activities that had more personal contact provided better outcomes. The Expert Working Group, composed of farm managers and pesticide handlers, was key to the identification of solutions, as were farm site visits. Audience participation, hands-on testing, and orchard field trials were particularly effective in the evaluation of potential solutions. Small work groups in a Regional Advisory Committee provided the best direction and guidance for a “user-friendly” translational document that provided evidence-based practical solutions. The “farmer to farmer” format of the guide was endorsed by both the Expert Working Group and the Regional Advisory Committee. Managers and pesticide handlers wanted to share their solutions in order to “help others stay safe,” and they appreciated attribution in the guide. The guide is now being used in educational programs across the region. The fundamental concept that farmers and farmworkers are innovators and experts in agricultural production was affirmed by this study. The success of this process demonstrates the value of participatory industrial hygiene in agriculture. 相似文献
ABSTRACTForest workers, including loggers, foresters, and wildland firefighters, are regularly exposed to some of the most fatal occupational environments in the United States. These hazardous work environments may become even more complex and dynamic when subject to bark beetle outbreaks that have resulted in significant tree mortality. The impacts of tree death from bark beetles are significant, with the cumulative 17-year (2000–2016) footprint for bark beetle caused tree mortality estimated at 54 million acres. However, how workers think about and act in these environments is understudied. This study, therefore, approaches the issue of beetle kill and forest worker safety by examining the perspectives or workers themselves. Its contribution is to leverage ethnographic research to provide insights that can generate new research questions, better inform outreach, and ultimately improve worker safety outcomes. The resulting insights show that beetle kill was understood by workers as a hazard that increased the complexity and dynamism of the work environment, making situational awareness both more necessary and more difficult to maintain. While much research about situational awareness focuses on hazardous situations, it is suggested that building adequate situational awareness should also include broader considerations of organizational communication, as well as training and experience considered over the course of entire careers. 相似文献