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A variety of acute brain insults can induce epileptogenesis, a complex process that results in acquired epilepsy. Despite advances in understanding mechanisms of epileptogenesis, there is currently no approved treatment that prevents the development or progression of epilepsy in patients at risk. The current concept of epileptogenesis assumes a window of opportunity following acute brain insults that allows intervention with preventive treatment. Recent results suggest that injury-induced epileptogenesis can be a much more rapid process than previously thought, suggesting that the 'therapeutic window' may only be open for a brief period, as in stroke therapy. However, experimental data also suggest a second, possibly delayed process ("secondary epileptogenesis") that influences the progression and refractoriness of the epileptic state over time, allowing interfering with this process even after onset of epilepsy. In this review, both methodological issues in preclinical drug development and novel targets for antiepileptogenesis will be discussed. Several promising drugs that either prevent epilepsy (antiepileptogenesis) or slow epilepsy progression and alleviate cognitive or behavioral comorbidities of epilepsy (disease modification) have been described in recent years, using diverse animal models of acquired epilepsy. Promising agents include TrkB inhibitors, losartan, statins, isoflurane, anti-inflammatory and anti-oxidative drugs, the SV2A modulator levetiracetam, and epigenetic interventions. Research on translational target validity and on prognostic biomarkers that can be used to stratify patients (or experimental animals) at high risk of developing epilepsy will hopefully soon lead to proof-of-concept clinical trials with the most promising drugs, which will be essential to make prevention of epilepsy a reality. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.
The Novel Cure Epub 11
The fusion oncogene, promyelocytic leukaemia (PML)-retinoic acid receptor-α (RARA), initiates acute promyelocytic leukaemia (APL) through both a block to differentiation and increased self-renewal of leukaemic progenitor cells. The current standard of care is retinoic acid (RA) and chemotherapy, but arsenic trioxide also cures many patients with APL, and an RA plus arsenic trioxide combination cures most patients. This Review discusses the recent evidence that reveals surprising new insights into how RA and arsenic trioxide cure this leukaemia, by targeting PML-RARα for degradation. Drug-triggered oncoprotein degradation may be a strategy that is applicable to many cancers.
Proportion of patients with virological cure (negative nasopharyngeal PCR) by day, in COVID-19 patients treated with hydroxychloroquine only, in COVID-19 patients treated with hydroxychloroquine and azithromycin combination, and in COVID-19 control patients.
Thyrotoxicosis is a common disorder, especially in women. The most frequent cause is Graves' disease (autoimmune hyperthyroidism). Other important causes include toxic nodular hyperthyroidism, due to the presence of one or more autonomously functioning thyroid nodules, and thyroiditis caused by inflammation, which results in release of stored hormones. Antithyroid drugs are the usual initial treatment (thionamides such as carbimazole or its active metabolite methimazole are the drugs of choice). A prolonged course leads to remission of Graves' hyperthyroidism in about a third of cases. Because of the low remission rate in Graves' disease and the inability to cure toxic nodular hyperthyroidism with antithyroid drugs alone, radioiodine is increasingly used as first line therapy, and is the preferred choice for relapsed Graves' hyperthyroidism. Total thyroidectomy is an option in selected cases. Future efforts are likely to concentrate on novel and safe ways to modulate the underlying disease process rather than stopping excess thyroid hormone production.
A novel CARM1-HuR axis involved in muscle differentiation and plasticity misregulated in spinal muscular atrophy. Ravel-Chapuis A, Haghandish A, Daneshvar N, Jasmin BJ, Côté J. Hum Mol Genet. 2021 Nov 15:ddab333. doi: 10.1093/hmg/ddab333. Online ahead of print.PMID: 34791230
Intraperitoneal delivery of a novel drug-like compound improves disease severity in severe and intermediate mouse models of Spinal Muscular Atrophy. Osman EY, Rietz A, Kline RA, Cherry JJ, Hodgetts KJ, Lorson CL, Androphy EJ. Sci Rep. 2019 Feb 7;9(1):1633. doi: 10.1038/s41598-018-38208-9.
The Spinal Muscular Atrophy Health Index: A novel outcome for measuring how a patient feels and functions. Muscle Nerve. Zizzi CE, Luebbe E, Mongiovi P, Hunter M, Dilek N, Garland C, Ciafaloni E, Zaidman CM, Kissel JT, McDermott MP, Johnson N, Sansone V, Heatwole CR. 2021 Jun;63(6):837-844. doi: 10.1002/mus.27223. Epub 2021 Mar 24. PMID: 33711174.
A Body of Practical Divinity, or A Christian Directory, Volume 5. (569 pages)[pdf epub mobi txt web via Google Books]This volume contains part 4: Christian Politics (or, Duties to Our Rulers and Neighbours)
Full and Easy Satisfaction Which is True and Safe Religion. (220 pages)[pdf epub mobi txt web via Internet Archive]A conference between a doubter, a papist, and a reformed believer.
Monthly Preparations for the Holy Communion. (182 pages)[pdf epub mobi txt web via Internet Archive]Appended with meditations for before and after receiving communion, and hymns.
The Practical Works of Richard Baxter, Volume 2. (616 pages)[pdf epub mobi txt web via Internet Archive]This volume contains part 1 of A Christian Directory (already listed in greater detail above): Christian Ethics.
The Practical Works of Richard Baxter, Volume 4. (512 pages)[pdf epub mobi txt web via Internet Archive]This volume contains part 2 of A Christian Directory (already listed in greater detail above): Christian Economics (or, Family Duties).
The Practical Works of Richard Baxter, Volume 5. (638 pages)[pdf epub mobi txt web via Internet Archive]This volume contains part 3 of A Christian Directory (already listed in greater detail above): Christian Ecclesiastics (or, Church Duties).
The Practical Works of Richard Baxter, Volume 6. (576 pages)[pdf epub mobi txt web via Internet Archive]This volume contains part 4 of A Christian Directory (already listed in greater detail above): Christian Politics (or, Duties to Our Rulers and Neighbours).
A Sermon of Judgment. (424 pages)[pdf epub mobi txt web via Internet Archive]From a sermon on 2 Corinthians 5:10-11, which was originally preached December 17, 1654, but which is here enlarged upon.
Despite extraordinary progress in helping people with CF live longer and healthier lives, there is still critical work to be done to help all people living with this disease, including those who won't benefit from modulators such as Trikafta. The Cystic Fibrosis Foundation's $500 million Path to a Cure is focused on developing new treatments for the underlying cause of the disease and, one day, a cure. This initiative centers around three core strategies to address the underlying cause of CF: repairing broken CFTR protein, restoring CFTR protein when none exists, and fixing or replacing the underlying genetic mutation to address the root cause of CF.
The Feature Paper can be either an original research article, a substantial novel research study that often involvesseveral techniques or approaches, or a comprehensive review paper with concise and precise updates on the latestprogress in the field that systematically reviews the most exciting advances in scientific literature. This type ofpaper provides an outlook on future directions of research or possible applications.
Bar DZ, Atkatsh K, Tavarez U, Erdos MR, Gruenbaum Y, Collins FS. Biotinylation by antibody recognition- A novel method for proximity labeling. BioRxiv 069187 [Preprint]. 2016 [cited 2017 Jan 12]. Available from:
Discovery of a novel proteasome inhibitor selective for cancer cells over non-transformed cells.Kazi A, Lawrence H, Guida WC, McLaughlin ML, Springett GM, Berndt N, Yip RM, Sebti SM.Cell Cycle. 2009 Jun 15;8(12):1940-51. Epub 2009 Jun 20.
Superselective intra-arterial cerebral infusion of novel agents after blood-brain disruption for the treatment of recurrent glioblastoma multiforme: a technical case series. Shin BJ, Burkhardt JK, Riina HA, Boockvar JA. Neurosurg Clin N Am. 2012 Apr;23(2):323-9. Epub 2012 Feb 18. PubMed PMID: 22440875.
Important to understanding these diseases has been our development, characterization and utilization of mouse models of disease for SARS-CoV, MERS-CoV and SARS-CoV-2. The rapid and successful development of these models has allowed us to unravel the cellular and physiological basis for disease of these viruses. In addition, the creation of these models has allowed for therapeutic development of vaccines, antibodies, small molecules, novel and repurposed drugs and other therapeutics. Critical to my research is the synergy of our in vitro and in vivo models of disease that allow us deep understandings of how these viruses work. 2ff7e9595c
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