6% decrease in accuracy for all memory loads. Placebo effects occurred as a function of working memory capacity, with individuals with high working memory capacity experiencing less severe placebo-related impairment compared with those with low working memory capacity. Our results demonstrate that severity of topiramate-related cognitive deficits occurs as a function of both drug exposure and baseline cognitive function. By identifying patient- and exposure-related characteristics that modulate the severity of cognitive side effects, topiramate dosing strategies may be individually tailored in the future to prevent unwanted cognitive impairment. © 2020, The American College of Clinical Pharmacology.Small heat shock proteins (sHSPs) are an ubiquitous protein family found in archaea, bacteria and eukaryotes. In plants, as in other organisms, sHSPs are upregulated by stress and are proposed to act as molecular chaperones to protect other proteins from stress-induced damage. sHSPs share an 'α-crystallin domain' with a β-sandwich structure and a diverse N-terminal domain. Although sHSPs are 12-25 kDa polypeptides, most assemble into oligomers with ≥ 12 subunits. Plant sHSPs are particularly diverse and numerous; some species have as many as 40 sHSPs. In angiosperms this diversity comprises ≥ 11 sHSP classes encoding proteins targeted to the cytosol, nucleus, endoplasmic reticulum, chloroplasts, mitochondria and peroxisomes. The sHSPs underwent a lineage-specific gene expansion, diversifying early in land plant evolution, potentially in response to stress in the terrestrial environment, and expanded again in seed plants and again in angiosperms. Understanding the structure and evolution of plant sHSPs has progressed, and a model for their chaperone activity has been proposed. However, how the chaperone model applies to diverse sHSPs and what processes sHSPs protect are far from understood. As more plant genomes and transcriptomes become available, it will be possible to explore theories of the evolutionary pressures driving sHSP diversification. © 2020 The Authors. New Phytologist © 2020 New Phytologist Trust.The incidence of migraine is higher among women than men and peaks during the reproductive years, when contraceptive medication use is common. Atogepant, a potent, selective antagonist of the calcitonin gene-related peptide receptor-in development for migraine prevention-is thus likely to be used by women taking oral contraceptives. This phase 1, open-label, single-center, 2-period, fixed-sequence study examined the effect of multiple-dose atogepant 60 mg once daily on the single-dose pharmacokinetics of a combination oral contraceptive, ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg (EE/LNG), in healthy postmenopausal or oophorectomized women. For participants in period 1, a single dose of EE/LNG was followed by a 7-day washout. In period 2, atogepant was given once daily on days 1-17; an oral dose of EE/LNG was coadministered with atogepant on day 14. Plasma pharmacokinetic parameters for EE and LNG were assessed following administration with and without atogepant. Twenty-six participants aged 45-64 years enrolled; 22 completed the study in accordance with the protocol. The area under the concentration-time curve extrapolated to infinity (AUC0-∞ ) of LNG was increased by 19% when administered with atogepant. Coadministration of atogepant and a single dose of EE/LNG did not substantially alter the pharmacokinetics of EE; the ∼19% increase in plasma AUC0-∞ of LNG is not anticipated to be clinically significant. Overall, atogepant alone and in combination with EE/LNG was generally well tolerated, with no new safety signals identified. © 2020 Merck Sharp & Dohme Corp. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.OBJECTIVE Deep brain stimulation (DBS) is an increasingly applied treatment for various neuropsychiatric disorders including drug-resistant epilepsy, and it may be optimized by rationalizing the stimulation protocol based on increased knowledge of its mechanism of action. We evaluated the effects of minutes to hours of hippocampal DBS on hippocampal evoked potentials (EPs) and local field potentials (LFPs) in freely moving male rats to further investigate some of the previously proposed mechanisms of action. METHODS Hippocampal high-frequency (130 Hz) DBS was administered for 0, 1, or 6 min every 10 min for 160 min. Stimulation parameter settings were similar to those that had previously been shown to reduce seizures in epileptic rats. EPs and LFPs were recorded in the stimulation-free intervals. We investigated both the immediate temporary effects of 1 or 6 min of DBS and the effects of 160 min of intermittent DBS. Input specificity was investigated by using two different stimulation electrodes. RESULTS Relarmittent DBS-as typically used in epilepsy patients-as an alternative to continuous DBS. © 2020 International League Against Epilepsy.BACKGROUND Following the demonstration of efficacy of hydroxychloroquine against SARS-CoV-2 in-vitro, many trials started to evaluate its efficacy in clinical settings. However, no systematic review and meta-analysis has addressed the issue of safety and efficacy of hydroxychloroquine (HCQ) in COVID-19. METHODS We conducted a systematic review and metaanalysis with the objectives of evaluation of safety and efficacy of HCQ alone or in combination in terms of "time to clinical cure", "virological cure", "death or clinical worsening of disease", "radiological progression" and safety. RevMan was used for meta-analysis. RESULT We searched 16 literature databases out of which seven studies (n=1358) were included in the systematic review. In terms of clinical cure, 2 studies reported possible benefit in "time to body temperature normalization" and one study reported less "cough days" in the HCQ arm. Treatment with HCQ resulted in less number of cases showing radiological progression of lung disease (OR 0.31, 0.11-0.9). No difference was observed in virological cure (OR 2.37, 0.13-44.53), death or clinical worsening of disease (OR 1.37, 1.37-21.97) and safety (OR 2.19, 0.59-8.18), when compared to the control/conventional treatment. Five studies reported either the safety or efficacy of HCQ + Azithromycin. Although seems safe and effective, more data is required for a definitive conclusion. CONCLUSION HCQ seems to be promising in terms of less number of cases with radiological progression with a comparable safety profile to control/conventional treatment. We need more data to come to a definite conclusion. This article is protected by copyright. https://www.selleckchem.com/products/gdc-0068.html All rights reserved. This article is protected by copyright. All rights reserved.