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1.
Katja Kobow Christopher A. Reid Erwin A. van Vliet Albert J. Becker Gemma L. Carvill Alica M. Goldman Shinichi Hirose Iscia Lopes-Cendes Hela Mrabet Khiari Annapurna Poduri Michael R. Johnson David C. Henshall 《Epileptic Disord》2020,22(2):127-141
Epigenetics refers broadly to processes that influence medium to long‐term gene expression by changing the readability and accessibility of the genetic code. The Neurobiology Commission of the International League Against Epilepsy (ILAE) recently convened a Task Force to explore and disseminate advances in epigenetics to better understand their role and intersection with genetics and the neurobiology of epilepsies and their co‐morbidities, and to accelerate translation of these findings into the development of better therapies. Here, we provide a topic primer on epigenetics, explaining the key processes and findings to date in experimental and human epilepsy. We review the growing list of genes with epigenetic functions that have been linked with epilepsy in humans. We consider potential practical applications, including using epigenetic signals as biomarkers for tissue‐ and biofluid‐based diagnostics and the prospects for developing epigenetic‐based treatments for epilepsy. We include a glossary of terms, FAQs and other supports to facilitate a broad understanding of the topic for the non‐expert. Last, we review the limitations, research gaps and the next challenges. In summary, epigenetic processes represent important mechanisms controlling the activity of genes, providing opportunities for insight into disease mechanisms, biomarkers and novel therapies for epilepsy. 相似文献
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Famke L. Schneiders Charlotte M. Huijts Martine Reijm Hetty J. Bontkes Henk M.W. Verheul Tanja D. de Gruijl Hans J. van der Vliet 《Immunobiology》2018,223(2):171-177
Aminobisphosphonates (NBP) are used for treatment of metastatic bone disease. Frequently, patients undergoing NBP-treatment experience side-effects, known as acute phase response (APR), resulting from cytokine production by Vγ9Vδ2-T cells. As opposed to NBP, statins reduce intracellular phosphoantigen levels and prevent NBP-induced Vγ9Vδ2-T cell activation in vitro. We conducted a pilot study in patients with (bone-)metastasized malignancies receiving NBP-treatment and evaluated the phenotype and function of circulating Vγ9Vδ2-T cells in vivo and the effects of statins on Vγ9Vδ2-T cell responses and the associated APR. We observed reduced expression of perforin, granzyme B and HLA-DR on Vγ9Vδ2-T cells in patients treated with NBP and statins. However, statins could not prevent NBP-induced changes in circulating Vγ9Vδ2-T cell numbers or production of IFNγ and TNFα. Consistent with this, simvastatin could not prevent the occurrence of APR upon NBP-infusion. These observations call for the exploration of alternative strategies to prevent collateral APR upon NBP treatment. 相似文献
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Alan M. Springer Gus B. van Vliet 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(18):E1880-E1888
Climate change in the last century was associated with spectacular growth of many wild Pacific salmon stocks in the North Pacific Ocean and Bering Sea, apparently through bottom-up forcing linking meteorology to ocean physics, water temperature, and plankton production. One species in particular, pink salmon, became so numerous by the 1990s that they began to dominate other species of salmon for prey resources and to exert top-down control in the open ocean ecosystem. Information from long-term monitoring of seabirds in the Aleutian Islands and Bering Sea reveals that the sphere of influence of pink salmon is much larger than previously known. Seabirds, pink salmon, other species of salmon, and by extension other higher-order predators, are tightly linked ecologically and must be included in international management and conservation policies for sustaining all species that compete for common, finite resource pools. These data further emphasize that the unique 2-y cycle in abundance of pink salmon drives interannual shifts between two alternate states of a complex marine ecosystem.Predator control of community structure and ecosystem function became a tenet of intertidal and nearshore marine ecology following early studies of Paine and others (1–3), yet with few exceptions (4, 5), until more recent times the idea has been less well appreciated for open oceans. Growing attention now is being paid to the overexploitation of pelagic species, particularly those at higher trophic levels currently and in the past, and effects on ocean ecosystems of the loss, or development, of top-down forcing (6–12).The prevailing view has long held that most biological change in ocean ecosystems, apart from human exploitation, is driven from the bottom up (13–16). One striking example that has been linked to bottom-up processes driven by climate change is the burgeoning abundance of wild Pacific salmon (Oncorhynchus spp.), and in particular pink salmon (Oncorhynchus gorbuscha), in the subarctic North Pacific Ocean and Bering Sea (SNPO/BS). Underpinning the notion initially were studies that found (i) strong coherence between decadal patterns in the Aleutian Low pressure system, which exerts a large influence over climate in the North Pacific Ocean, and patterns in salmon production across a broad region of the SNPO/BS (17, 18); (ii) decadal patterns in primary production that could be explained by the effect of the Aleutian Low pressure system on basin scale wind fields (19); and (iii) decadal patterns in zooplankton, squid, and pelagic fish production that also were correlated with meteorological forcing over the North Pacific Ocean and consistent with patterns in primary production (20). Thus, the general explanation for waxing and waning abundances of salmon over the record in the 20th century was that physical forcing by shifts in the strength and position of the Aleutian Low altered winds, ocean temperatures, and primary and secondary production to the benefit or detriment of salmon. A decadal scale oscillation in the Aleutian Low, now often referred to as the Pacific Decadal Oscillation (PDO) (21), has been linked to numerous physical and biological variability in the SNPO/BS in addition to salmon abundance (21–23).It was subsequently shown that salmon population responses and their relation to the PDO were out of phase between Alaska and the northwest coast of North America during much of the 20th century (24); that warm anomalies in coastal temperatures were associated with increased survival of salmon in Alaska; and that regional-scale variability in ocean temperature was a better predictor of salmon survival than large, basin-scale variability characterized by the PDO (25). A recent analysis from around the rim of the North Pacific Ocean found regional covariance in abundance of pink salmon, chum salmon (Oncorhynchus keta), and sockeye salmon (Oncorhynchus nerka) associated with the Aleutian Low, and with smaller scale spatially coherent, but regionally distinct, patterns in climate (26).Water temperature can be important to the early growth and survival of pink salmon fry directly by its effect on physiology and indirectly by its effect on the timing and development of zooplankton prey stocks in nursery areas, which commonly is advanced and greater in warmer years than in cooler years. In cooler springs, fry grow more slowly and a greater number die both from lack of food and from an increased susceptibility to predators (27, 28). For example, a conceptual model for Prince William Sound, Alaska, holds that, in years of abundant spring zooplankton, fry grow faster and remain longer in the shelter of inshore nurseries where they are protected from walleye pollock (Theragra chalcogramma) and Pacific herring (Clupea pallasii), two chief predators that remain offshore feeding primarily on swarms of large calanoid copepods and other macrozooplankton. In cooler years of lower zooplankton biomass inshore, fry grow more slowly, move offshore earlier, and suffer higher predation by pollock and herring due to spatial overlap, smaller size, and less alternative prey for those two predators (28).Although the relationship between climate and pink salmon survival is likely complex, fluctuations in abundance appear to be modulated in large measure directly and indirectly by the thermal environment in which a stock lives. Such a fundamentally bottom-up explanation is bolstered by observations of high growth and survival rates of pink salmon during the period of warmer ocean temperatures and population increase (29, 30), and at this time provides a more parsimonious explanation for population dynamics than would explanations invoking strictly top-down control across such a broad region. Now, however, several lines of evidence indicate that pink salmon themselves are having a large top-down influence on other salmon species, other upper trophic level pelagic species, plankton standing stocks, and by inference, the functioning of the open-ocean ecosystem in the SNPO/BS. 相似文献
7.
van de Vliet P Onghena P Knapen J Fox KR Probst M van Coppenolle H Pieters G 《Disability and rehabilitation》2003,25(24):1344-1353
Purpose: Exercise has been put forward as a therapeutic means for the treatment of clinical depression.
Methods: In this study, 29 patients, all with diagnosed with mood disorder, completed daily measurements of depression and physical well-being during periods ranging from 77 to 436 days (M = 146.5). Fitness training was added to the treatment after a period and changes before (A-phase) and after (B-phase) the implementation of this training were the subject of investigation. Data were analysed by means of randomization tests with an AB-design and time-series analysis. Replication of the findings was investigated using Fisher's multiplicative method.
Results: Adding fitness training to the treatment of clinical depression does not systematically lead to changes in self-reported feelings of depression on top of benefits that may be due to other treatments.
Conclusion: Since the present findings are not in agreement with previous studies, the absence of statistically significant changes in self-reported feelings of depression is discussed within the complexity of the 'exercise - depression' relationship in inpatient populations. These included the severity of their depression, the potential ceiling effect of a multifaceted treatment programme and the initial increase in depression due to the confrontational nature of the intervention. 相似文献
Methods: In this study, 29 patients, all with diagnosed with mood disorder, completed daily measurements of depression and physical well-being during periods ranging from 77 to 436 days (M = 146.5). Fitness training was added to the treatment after a period and changes before (A-phase) and after (B-phase) the implementation of this training were the subject of investigation. Data were analysed by means of randomization tests with an AB-design and time-series analysis. Replication of the findings was investigated using Fisher's multiplicative method.
Results: Adding fitness training to the treatment of clinical depression does not systematically lead to changes in self-reported feelings of depression on top of benefits that may be due to other treatments.
Conclusion: Since the present findings are not in agreement with previous studies, the absence of statistically significant changes in self-reported feelings of depression is discussed within the complexity of the 'exercise - depression' relationship in inpatient populations. These included the severity of their depression, the potential ceiling effect of a multifaceted treatment programme and the initial increase in depression due to the confrontational nature of the intervention. 相似文献
8.
Kam BL Teunissen JJ Krenning EP de Herder WW Khan S van Vliet EI Kwekkeboom DJ 《European journal of nuclear medicine and molecular imaging》2012,39(Z1):S103-S112
Treatment with radiolabelled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumours. Symptomatic improvement may occur with (177)Lu-labelled somatostatin analogues that have been used for peptide receptor radionuclide therapy (PRRT). The results obtained with (177)Lu-[DOTA(0),Tyr(3)]octreotate (DOTATATE) are very encouraging in terms of tumour regression. Dosimetry studies with (177)Lu-DOTATATE as well as the limited side effects with additional cycles of (177)Lu-DOTATATE suggest that more cycles of (177)Lu-DOTATATE can be safely given. Also, if kidney-protective agents are used, the side effects of this therapy are few and mild and less than those from the use of (90)Y-[DOTA(0),Tyr(3)]octreotide (DOTATOC). Besides objective tumour responses, the median progression-free survival is more than 40 months. The patients' self-assessed quality of life increases significantly after treatment with (177)Lu-DOTATATE. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with (177)Lu-DOTATATE. These findings compare favourably with the limited number of alternative therapeutic approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable neuroendocrine tumours. 相似文献
9.
What do people appreciate in physicians' communication? An international study with focus groups using videotaped medical consultations 下载免费PDF全文
Maria A. Mazzi MSc Michela Rimondini PhD Myriam Deveugele PhD Christa Zimmermann PhD Francesca Moretti PhD Liesbeth van Vliet PhD Giuseppe Deledda MSc Ian Fletcher PhD Jozien Bensing PhD 《Health expectations》2015,18(5):1215-1226