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In determining which patients should be offered front-line maintenance PARP inhibitors, and which agent to use, there are multiple factors to consider, including FDA indication, dosing preference, toxicity, risks versus benefits for each patient population, and cost. There are ongoing studies further exploring the front-line use of PARP inhibitors, including the potential downstream effects of PARP-inhibitor resistance in the recurrent setting, combining PARP-inhibitors with other anti-angiogenic drugs, immunotherapeutic agents, and inhibitors of pathways implicated in PARP inhibitor resistance.

Inflammatory autoimmune diseases are chronic diseases that often affect women of childbearing age. Therefore, detailed knowledge of the safety profile of medications used for management of inflammatory autoimmune diseases during pregnancy is important. However, in many cases the potential harmful effects of medications (especially biologics) during pregnancy (and lactation) on mother and child have not been fully identified.

Our aim was to update the data on the occurrence of miscarriages and (major) congenital malformations when using biologics during pregnancy based on newly published articles. Additionally, we selected several different secondary outcomes that may be of interest for clinicians, especially information on adverse events in the use of a specific biologic during pregnancy.

A search was conducted from 1 January 2015 until 4 July 2019 in Embase.com, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar with specific search terms for each database. Selection of publications was based on title/abstract and followed by full text (double blinded, two researchers). this website An overview was made based on outcomes of interest. References of the included publications were reviewed to include and minimize the missing publications.

A total of 143 publications were included. The total number of cases ranged from nine for canakinumab to 4276 for infliximab. The rates of miscarriages and major congenital malformations did not show relevant differences from those rates in the general population.

Despite limitations to our study, no major safety issues were reported and no trend could be identified in the reported malformations.

Despite limitations to our study, no major safety issues were reported and no trend could be identified in the reported malformations.Vadadustat (VAFSEO®) is a prolyl hydroxylase inhibitor being developed by Akebia Therapeutics, Inc. (Akebia) for the treatment of anaemia associated with chronic kidney disease (CKD). Akebia is collaborating with Mitsubishi Tanabe Pharma Corporation on the development and commercialization of vadadustat in Japan and with Otsuka Pharmaceutical Co. Ltd on the development and commercialization of vadadustat in the USA, the EU and certain other territories. The drug is approved in Japan for use in adult patients with anaemia associated with CKD and regulatory submissions are planned in the USA and the EU. This article summarizes the milestones in the development of vadadustat leading to this first approval.Fostemsavir (Rukobia), a prodrug of the HIV-1 attachment inhibitor temsavir, is a first-in-class treatment for HIV infection being developed by ViiV Healthcare. Based on the results of the phase III BRIGHTE trial fostemsavir was recently approved in the USA for the treatment of patients with HIV not able to be treated with other therapies. This article summarizes the milestones in the development of fostemsavir leading to this first approval.The neural mechanisms of sleep, a fundamental biological behavior from invertebrates to humans, have been a long-standing mystery and present an enormous challenge. Gradually, perspectives on the neurobiology of sleep have been more various with the technical innovations over the recent decades, and studies have now identified many specific neural circuits that selectively regulate the initiation and maintenance of wake, rapid eye movement (REM) sleep, and non-REM (NREM) sleep. The cholinergic system in basal forebrain (BF) that fire maximally during waking and REM sleep is one of the key neuromodulation systems related to waking and REM sleep. Here we outline the recent progress of the BF cholinergic system in sleep-wake cycle. The intricate local connectivity and multiple projections to other cortical and subcortical regions of the BF cholinergic system elaborately presented here form a conceptual framework for understanding the coordinating effects with the dissecting regions. This framework also provides evidences regarding the relationships between the general anesthesia and wakefulness/sleep cycle focusing on the neural circuitry of unconsciousness induced by anesthetic drugs.The hippocampus is critical for spatial navigation. In this review, we focus on the role of the hippocampus in three basic strategies used for spatial navigation path integration, stimulus-response association, and map-based navigation. First, the hippocampus is not required for path integration unless the path of path integration is too long and complex. The hippocampus provides mnemonic support when involved in the process of path integration. Second, the hippocampus’s involvement in stimulus-response association is dependent on how the strategy is conducted. The hippocampus is not required for the habit form of stimulus-response association. Third, while the hippocampus is fully engaged in map-based navigation, the shared characteristics of place cells, grid cells, head direction cells, and other spatial encoding cells, which are detected in the hippocampus and associated areas, offer a possibility that there is a stand-alone allocentric space perception (or mental representation) of the environment outside and independent of the hippocampus, and the spatially specific firing patterns of these spatial encoding cells are the unfolding of the intermediate stages of the processing of this allocentric spatial information when conveyed into the hippocampus for information storage or retrieval. Furthermore, the presence of all the spatially specific firing patterns in the hippocampus and the related neural circuits during the path integration and map-based navigation support such a notion that in essence, path integration is the same allocentric space perception provided with only idiothetic inputs. Taken together, the hippocampus plays a general mnemonic role in spatial navigation.