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Unlucky numbers: Fighting murder convictions that rest on shoddy stats
LEIDEN, THE NETHERLANDS— When a Dutch nurse named Lucia de Berk stood trial for serial murder in 2003, statistician Richard Gill was aware of the case. But he saw no reason to stick his nose into it. De Berk was a pediatric nurse at Juliana Children’s Hospital in The Hague. In 2001, after a baby died while she was on duty, a colleague told superiors that De Berk had been present at a suspiciously high number of deaths and resuscitations. Hospital staff immediately informed the police. When investigators reexamined records from De Berk’s shifts, they found 10 suspicious incidents. Three other hospitals where D...
Source: Science of Aging Knowledge Environment - January 19, 2023 Category: Geriatrics Source Type: research

Protective Effect of Ergothioneine Against Stroke in Rodent Models
AbstractErgothioneine (ET) is a naturally occurring antioxidant and cytoprotective agent that is synthesized by fungi and certain bacteria. Recent studies have shown a beneficial effect of ET on neurological functions, including cognition and animal models of depression. The aim of this study is to elucidate a possible effect of ET in rodent models of stroke. Post-ischemic intracerebroventricular (i.c.v.) infusion of ET significantly reduced brain infarct volume by as early as 1  day after infusion in rats, as shown by triphenyltetrazolium chloride (TTC) assay. There was a dose-dependent increase in protection, from 50 to...
Source: NeuroMolecular Medicine - October 19, 2022 Category: Neurology Source Type: research

Loop Diuretics Inhibit Ischemia-Induced Intracellular Ca2+ Overload in Neurons via the Inhibition of Voltage-Gated Ca2+ and Na+ Channels
One consequence of ischemic stroke is disruption of intracellular ionic homeostasis. Intracellular overload of both Na+ and Ca2+ has been linked to neuronal death in this pathophysiological state. The etiology of ionic imbalances resulting from stroke-induced ischemia and acidosis includes the dysregulation of multiple plasma membrane transport proteins, such as increased activity of sodium-potassium-chloride cotransporter-1 (NKCC-1). Experiments using NKCC1 antagonists, bumetanide (BMN) and ethacrynic acid (EA), were carried out to determine if inhibition of this cotransporter affects Na+ and Ca2+ overload observed follow...
Source: Frontiers in Pharmacology - September 15, 2021 Category: Drugs & Pharmacology Source Type: research

Behavioral and histopathological consequences of transient ischemic stroke in the Flinders Sensitive Line rat, a genetic animal model of depression
Brain Res. 2021 Sep 4:147648. doi: 10.1016/j.brainres.2021.147648. Online ahead of print.ABSTRACTPatients with depression have an increased risk for stroke, higher mortality rates following stroke and worse functional outcomes among survivors. Preclinical studies may help to better understand the underlying mechanisms linking these two diseases, but only a few animal studies have investigated the effects of prestroke depression. The present study investigates whether Flinders Sensitive Line (FSL) rats, a genetic depression model, respond differently to focal ischemic stroke compared to control strains (Flinders Resistant L...
Source: Brain Research - September 7, 2021 Category: Neurology Authors: Denise F Happ Gregers Wegener R Andrew Tasker Source Type: research

Interleukin-18 from neurons and microglia mediates depressive behaviors in mice with post-stroke depression.
In this study, we demonstrate that in IL-18 level in the ischemic brain significantly increased in mice with depression-like behaviors that caused by the combined use of chronic spatial restraint stress and middle cerebral artery occlusion. Interestingly, IL-18 expression was mainly found in neurons at early phase and in microglia in late phase. Injection of exogenous IL-18 in to the amygdala, but not the hippocampus or the striatum, caused severe depression-like behaviors. On the contrary, the blockage of endogenous IL-18 by IL-18 binding protein, a specific antagonist of IL-18, rescued depressive phenotypes in SIR mice. ...
Source: Brain, Behavior, and Immunity - April 5, 2020 Category: Neurology Authors: Wu D, Zhang G, Zhao C, Yang Y, Miao Z, Xu X Tags: Brain Behav Immun Source Type: research

Flinders Sensitive Line rats are resistant to infarction following transient occlusion of the middle cerebral artery.
CONCLUSIONS: Our study suggests that the rat strain does not influence infarct volumes following MCAo. PMID: 32194078 [PubMed - as supplied by publisher]
Source: Brain Research - March 15, 2020 Category: Neurology Authors: Bay V, Happ DF, Ardalan M, Quist A, Oggiano F, Chumak T, Hansen K, Ding M, Mallard C, Andrew Tasker R, Wegener G Tags: Brain Res Source Type: research

Transcranial Direct Current Stimulation Use in Warfighting: Benefits, Risks, and Future Prospects
Conclusion The aim of this paper was to examine whether military tDCS use can be efficacious and ethical in military settings. Our assessment is that tDCS offers a number of cognitive, motor, and perceptual enhancement opportunities which could provide value in military situations like training and operations. There is potential scope for use in a number of key areas that directly affect practical battlefield advantage and survivability, such as deceptive capabilities, risk-taking, threat detection, perception, and physiological improvement. Additionally, tDCS has the potential to improve command and control decision maki...
Source: Frontiers in Human Neuroscience - April 17, 2019 Category: Neuroscience Source Type: research

The Discovery and Development of Liraglutide and Semaglutide
We describe one such approach, albumin binding, and explain how it was applied in the development of the human GLP-1 analog liraglutide once daily and, subsequently, semaglutide once weekly. The pharmacology of these two long-acting GLP-1 analogs, in terms of improving glycemic control, reducing body weight and decreasing cardiovascular (CV) risk, is also reviewed, together with some novel biology. In addition, we describe the importance of accurate target (GLP-1 receptor) tissue expression analysis. Now an established class of agents, GLP-1-based therapies represent a significant advance in the treatment of T2D. All curr...
Source: Frontiers in Endocrinology - April 11, 2019 Category: Endocrinology Source Type: research

Role of TREK-1 in Health and Disease, Focus on the Central Nervous System
Conclusion and Perspectives Since their cloning 20 years ago, the physiological importance of TREK-1 channels has continued to grow (Figure 3). Today, TREK-1 channels have been shown to be important and their presence is essential in a number of physiopathological processes. Their involvement in these different processes demonstrate the necessity to design pharmacological modulators, activators or inhibitors, of these channels to correct any TREK-1-related dysfunctions. Despites a number of studies and many molecule screenings, only few putative new drugs were identified. The activators belonging to the ML and BL series ...
Source: Frontiers in Pharmacology - April 10, 2019 Category: Drugs & Pharmacology Source Type: research

YiQiFuMai Powder Injection Attenuates Coronary Artery Ligation-Induced Heart Failure Through Improving Mitochondrial Function via Regulating ROS Generation and CaMKII Signaling Pathways
This study was carried out in accordance with the recommendations of “Guide for the Care and Use of Laboratory Animals, National Institutes of Health.” The protocol was approved by the “China Pharmaceutical University.” Surgical Preparation The mice were anesthetized with chloral hydrate (4% chloral hydrate, ip). The HF model was induced by CAL as previously reported (Gao et al., 2010). Successful ligation of the coronary artery was confirmed by the occurrence of ST-segment elevation in electrocardiogram. Sham operated mice were performed the same process except left CAL. After ligation, the h...
Source: Frontiers in Pharmacology - April 9, 2019 Category: Drugs & Pharmacology Source Type: research

Exposure to female estrous is beneficial for male mice against transient ischemic stroke.
CONCLUSION: Exposure to female estrous reduces mortality and improves functional recovery in MCAO male mice. The study provides the first evidence to support the importance of female interaction to male stroke rehabilitation. ABBREVIATIONS: GAP-43: growth-associated protein-43; SYP: Synaptophysin; MCAO: middle cerebral artery occlusion; OVXs: ovariectomies; CCA: common carotid artery; ECA: external carotid artery; EFE: estrous female exposure; TTC: 2,3,5-triphenyltetrazolium chloride; PAGE: polyacrylamide gel electrophoresis; PVDF: polyvinylidene difluoride; ANOVA: analysis of variance; LSD: least significant differenc...
Source: Neurological Research - March 1, 2019 Category: Neurology Tags: Neurol Res Source Type: research

Stable isotope labeling derivatization and magnetic dispersive solid phase extraction coupled with UHPLC-MS/MS for the measurement of brain neurotransmitters in post-stroke depression rats administrated with gastrodin.
Abstract Synchronous measurement of brain neurotransmitters and blood drug metabolism by dual sites in vivo microdialysis can provide very important information for several neurological disorders such as post-stroke depression (PSD). In this work, d0/d3-6-N-methyl-rhodamine 6G-N-hydroxysuccinimidyl formate (d0/d3-MRSF) were firstly designed, synthesized and used as stable isotope labeling derivatization reagents for the determination of multiple neurotransmitters by ultra-high performance liquid chromatography-tandem mass spectrometry. The light d0-MRSF was used to label neurotransmitters in real samples and the ...
Source: Analytica Chimica Acta - January 23, 2019 Category: Chemistry Authors: Zhao XE, He Y, Zhu S, Xu Y, You J, Bai Y, Liu H Tags: Anal Chim Acta Source Type: research