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Daratumumab is a human monoclonal antibody targeting CD38, an antigen uniformly expressed by plasma cells in multiple myeloma and light chain amyloidosis (AL). We report the results of a prospective multi-center, phase 2 study of daratumumab monotherapy in AL (NCT02816476). Forty previously treated AL patients with a difference between involved and uninvolved free light chains (dFLC) > 50 mg/L were included in 15 centers between 9/2016 and 4/2018. Patients received six 28-day cycles of IV daratumumab, QW for cycles 1-2 and Q2W for cycles 3-6. Median age was 69 years (range 45-83). Twenty-six patients had 2 or more organs involved with heart in 24 and renal in 26. Median time from diagnosis to enrollment was 23 months (IQR 4-122) with a median of 3 prior therapies (range 1-5). At data cut-off (09/2019), all patients discontinued therapy and 33 received the planned 6 cycles. Overall, 22 patients had hematological response and 19 patients (47.5%) achieved Very Good Partial Response (dFLC less then 40mg/l) or better. Median time to hematological response was 1 week. Patients with no response after 4 doses were unlikely to further respond. Renal and cardiac responses occurred in 8 and 7 patients, respectively. Daratumumab was well tolerated with no unexpected adverse events. With a median follow-up of 26 months, the 2-year overall survival rate was 74% (95% CI 62-81). Daratumumab monotherapy is associated with deep and rapid hematological responses in previously treated AL patients, with a good safety profile. Further studies of daratumumab in combination regimens are warranted. Copyright © 2020 American Society of Hematology.BACKGROUND Endometriosis is a gynaecological hormone-dependent disorder that is defined by histological lesions generated by the growth of endometrial-like tissue out of the uterus cavity, most commonly engrafted within the peritoneal cavity, although these lesions can also be located in distant organs. Endometriosis affects ~10% of women of reproductive age, frequently producing severe and, sometimes, incapacitating symptoms, including chronic pelvic pain, dysmenorrhea and dyspareunia, among others. Furthermore, endometriosis causes infertility in ~30% of affected women. Despite intense research on the mechanisms involved in the initial development and later progression of endometriosis, many questions remain unanswered and its aetiology remains unknown. Recent studies have demonstrated the critical role played by the relationship between the microbiome and mucosal immunology in preventing sexually transmitted diseases (HIV), infertility and several gynaecologic diseases. OBJECTIVE AND RATIONALE In this revivicious cycle responsible for the development of endometriosis. https://www.selleckchem.com/products/Novobiocin-sodium(Albamycin).html WIDER IMPLICATIONS Determining the aetiology of endometriosis is a challenging issue. Posing a new hypothesis on this subject provides the initial tool necessary to design future experimental, clinical and epidemiological research that could allow for a better understanding of the origin of this disease. Furthermore, advances in the understanding of its aetiology would allow the identification of new therapeutics and preventive actions. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail journals.permission@oup.com.Maternal depression during pregnancy is associated with elevated risk of anxiety and depression in offspring, but the mechanisms are incompletely understood. Here we conducted a neuroimaging follow-up of a prenatal birth cohort from the European Longitudinal Study of Pregnancy and Childhood (n = 131; 53% women, age 23-24) to test whether deviations from age-normative structural brain development in young adulthood may partially underlie this link. Structural brain age was calculated based on previously published neuroanatomical age prediction models using cortical thickness maps from healthy controls aged 6-89. Brain age gap was computed as the difference between chronological and structural brain age. Participants also completed self-report measures of anxiety and mood dysregulation. Further, mothers of a subset of participants (n = 103, 54% women) answered a self-report questionnaire in 1990-1992 about depressive symptoms during pregnancy. Higher exposure to maternal depressive symptoms in utero showed a linear relationship with elevated brain age gap, which showed a quadratic relationship with anxiety and mood dysregulation in the young adult offspring. Our findings suggest that exposure to maternal depressive symptoms in utero may be associated with accelerated brain maturation and that deviations from age-normative structural brain development in either direction predict more anxiety and dysregulated mood in young adulthood. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.In order to develop successful strategies for coral reef preservation, it is critical that the biology of both host corals and symbiotic algae are investigated. In the Ryukyu Archipelago, which encompasses many islands spread over approximately 500 km of the Pacific Ocean, four major populations of the coral Acropora digitifera have been studied using whole genome shotgun (WGS) sequence analysis (Shinzato et al. 2015). In contrast, the diversity of the symbiotic dinoflagellates associated with these A. digitifera populations is unknown. It is therefore unclear if these two core components of the coral holobiont share a common evolutionary history. This issue can be addressed for the symbiotic algal populations by studying the organelle genomes of their mitochondria and plastids. Here we analyzed WGS data from ∼150 adult A. digitifera, and by mapping reads to the available reference genome sequences, we extracted 2,250 sequences representing 15 organelle genes of Symbiodiniaceae. Molecular phylogenetic analyses of these mitochondrial and plastid gene sets revealed that A. digitifera from the southern Yaeyama islands harbor a different Symbiodiniaceae population than the islands of Okinawa and Kerama in the north, indicating that the distribution of symbiont populations partially matches that of the four host populations. Interestingly, we found that numerous single-nucleotide polymorphisms (SNPs) correspond to known RNA-edited sites in 14 of the Symbiodiniaceae organelle genes, with mitochondrial genes showing a stronger correspondence than plastid genes. These results suggest a possible correlation between RNA editing and SNPs in the two organelle genomes of symbiotic dinoflagellates. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
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