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Drug Discovery Today May 2020In the past decade we have seen two major Ebola virus outbreaks in Africa, the Zika virus in Brazil and the Americas and the current pandemic of coronavirus disease... (Review)
Review
In the past decade we have seen two major Ebola virus outbreaks in Africa, the Zika virus in Brazil and the Americas and the current pandemic of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is a strong sense of déjà vu because there are still no effective treatments. In the COVID-19 pandemic, despite being a new virus, there are already drugs suggested as active in in vitro assays that are being repurposed in clinical trials. Promising SARS-CoV-2 viral targets and computational approaches are described and discussed. Here, we propose, based on open antiviral drug discovery approaches for previous outbreaks, that there could still be gaps in our approach to drug discovery.
Topics: Angiotensin-Converting Enzyme 2; Animals; Antiviral Agents; Betacoronavirus; COVID-19; Chlorocebus aethiops; Computer Simulation; Coronavirus Infections; Drug Discovery; Drug Repositioning; Hemorrhagic Fever, Ebola; Humans; In Vitro Techniques; Middle East Respiratory Syndrome Coronavirus; Molecular Docking Simulation; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Severe acute respiratory syndrome-related coronavirus; SARS-CoV-2; Severe Acute Respiratory Syndrome; Spike Glycoprotein, Coronavirus; Vero Cells; Zika Virus Infection; COVID-19 Drug Treatment
PubMed: 32320852
DOI: 10.1016/j.drudis.2020.03.019 -
New Ideas in Psychology Apr 2023The experiences associated with remembering, including metamemory feelings about the act of remembering and attempts at remembering, are not often integrated into...
The experiences associated with remembering, including metamemory feelings about the act of remembering and attempts at remembering, are not often integrated into general accounts of memory. For example, David Rubin (2022) proposes a unified, three-dimensional conceptual space for mapping memory states, a map that does not systematically specify metamemory feelings. Drawing on Rubin's model, we define a distinct role for metamemory in relation to first-order memory content. We propose a fourth dimension for the model and support the proposal with conceptual, neurocognitive, and clinical lines of reasoning. We use the modified model to illustrate several cases, and show how it helps to conceptualize a new category of memory state: , exemplified by . We also caution not to assume that memory experience is directly correlated with or caused by memory content, an assumption Tulving (1989) labeled the .
PubMed: 38223256
DOI: 10.1016/j.newideapsych.2022.100995 -
Journal of Intelligence Jun 2023Curiosity during learning increases information-seeking behaviors and subsequent memory retrieval success, yet the mechanisms that drive curiosity and its accompanying...
Curiosity during learning increases information-seeking behaviors and subsequent memory retrieval success, yet the mechanisms that drive curiosity and its accompanying information-seeking behaviors remain elusive. Hints throughout the literature suggest that curiosity may result from a metacognitive signal-possibly of closeness to a not yet accessible piece of information-that in turn leads the experiencer to seek out additional information that will resolve a perceptibly small knowledge gap. We examined whether metacognition sensations thought to signal the likely presence of an as yet unretrieved relevant memory (such as familiarity or déjà vu) might be involved. Across two experiments, when cued recall failed, participants gave higher curiosity ratings during reported déjà vu (Experiment 1) or déjà entendu (Experiment 2), and these states were associated with increased expenditure of limited experimental resources to discover the answer. Participants also spent more time attempting to retrieve information and generated more incorrect information when experiencing these déjà vu-like states than when not. We propose that metacognition signaling of the possible presence of an as yet unretrieved but relevant memory may drive curiosity and prompt information-seeking that includes further search efforts.
PubMed: 37367514
DOI: 10.3390/jintelligence11060112 -
BJOG : An International Journal of... Jan 2022
Topics: COVID-19; Civil Defense; Climate Change; Communicable Disease Control; Communicable Diseases, Emerging; Female; Health Services Needs and Demand; Humans; Infectious Disease Transmission, Vertical; Pandemics; Pregnancy; Pregnancy Complications, Infectious; Public Health; SARS-CoV-2; Travel; Travel-Related Illness
PubMed: 34379870
DOI: 10.1111/1471-0528.16859 -
Annals of Neurology Nov 2023Familial mesial temporal lobe epilepsy (FMTLE) is an important focal epilepsy syndrome; its molecular genetic basis is unknown. Clinical descriptions of FMTLE vary...
OBJECTIVE
Familial mesial temporal lobe epilepsy (FMTLE) is an important focal epilepsy syndrome; its molecular genetic basis is unknown. Clinical descriptions of FMTLE vary between a mild syndrome with prominent déjà vu to a more severe phenotype with febrile seizures and hippocampal sclerosis. We aimed to refine the phenotype of FMTLE by analyzing a large cohort of patients and asked whether common risk variants for focal epilepsy and/or febrile seizures, measured by polygenic risk scores (PRS), are enriched in individuals with FMTLE.
METHODS
We studied 134 families with ≥ 2 first or second-degree relatives with temporal lobe epilepsy, with clear mesial ictal semiology required in at least one individual. PRS were calculated for 227 FMTLE cases, 124 unaffected relatives, and 16,077 population controls.
RESULTS
The age of patients with FMTLE onset ranged from 2.5 to 70 years (median = 18, interquartile range = 13-28 years). The most common focal seizure symptom was déjà vu (62% of cases), followed by epigastric rising sensation (34%), and fear or anxiety (22%). The clinical spectrum included rare cases with drug-resistance and/or hippocampal sclerosis. FMTLE cases had a higher mean focal epilepsy PRS than population controls (odds ratio = 1.24, 95% confidence interval = 1.06, 1.46, p = 0.007); in contrast, no enrichment for the febrile seizure PRS was observed.
INTERPRETATION
FMTLE is a generally mild drug-responsive syndrome with déjà vu being the commonest symptom. In contrast to dominant monogenic focal epilepsy syndromes, our molecular data support a polygenic basis for FMTLE. Furthermore, the PRS data suggest that sub-genome-wide significant focal epilepsy genome-wide association study single nucleotide polymorphisms are important risk variants for FMTLE. ANN NEUROL 2023;94:825-835.
Topics: Humans; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Epilepsy, Temporal Lobe; Genome-Wide Association Study; Seizures, Febrile; Magnetic Resonance Imaging; Electroencephalography; Syndrome; Hippocampus
PubMed: 37597255
DOI: 10.1002/ana.26765 -
The Lancet. Infectious Diseases Feb 20235 months into the monkeypox epidemic, there are no proven therapies and no comparative safety and efficacy data in the treatment of affected individuals. The question... (Review)
Review
5 months into the monkeypox epidemic, there are no proven therapies and no comparative safety and efficacy data in the treatment of affected individuals. The question remains whether we, as a scientific and medical community, will apply the lessons learned from the past decade of outbreaks that well conducted randomised controlled trials can be ethically, safely, and efficiently performed to guide clinical decision making so that the right drug is used for the right patient at the right time. Furthermore, the robust level of evidence from randomised controlled trials is highly relevant to advocating for equitable access to new treatments in low-income and middle-income countries. As with COVID-19, we need to pair optimal supportive care with rigorously designed double-blind randomised controlled trials to elucidate safe and effective therapies for monkeypox. The need remains for the funding and development of predesigned, adaptive trial protocols for diseases with epidemic or pandemic potential that can be timely pulled off the shelf and launched early in an outbreak, leveraging ready clinical trial networks and infrastructure for rapid discovery and implementation of new treatments.
Topics: Humans; COVID-19; Mpox (monkeypox); Double-Blind Method; Pandemics; Disease Outbreaks; Randomized Controlled Trials as Topic
PubMed: 36400066
DOI: 10.1016/S1473-3099(22)00722-8 -
The British Journal of General Practice... 2021
Topics: Health Status Disparities; Humans
PubMed: 33632678
DOI: 10.3399/bjgp21X714941 -
Journal of Occupational Health Jan 2020On 31 December 2019, the World Health Organization (WHO) received reports of pneumonia cases of unknown etiology in the city of Wuhan in Hubei Province, China. The agent...
On 31 December 2019, the World Health Organization (WHO) received reports of pneumonia cases of unknown etiology in the city of Wuhan in Hubei Province, China. The agent responsible was subsequently identified as a coronavirus-SARS-CoV-2. The WHO declared this disease as a Public Health Emergency of International Concern at the end of January 2020. This event evoked a sense of déjà vu, as it has many similarities to the outbreak of severe acute respiratory syndrome (SARS) of 2002-2003. Both illnesses were caused by a zoonotic novel coronavirus, both originated during winter in China and both spread rapidly all over the world. However, the case-fatality rate of SARS (9.6%) is higher than that of COVID-19 (<4%). Another zoonotic novel coronavirus, MERS-CoV, was responsible for the Middle East respiratory syndrome, which had a case-fatality rate of 34%. Our experiences in coping with the previous coronavirus outbreaks have better equipped us to face the challenges posed by COVID-19, especially in the health care setting. Among the insights gained from the past outbreaks were: outbreaks caused by viruses are hazardous to healthcare workers; the impact of the disease extends beyond the infection; general principles of prevention and control are effective in containing the disease; the disease poses both a public health as well as an occupational health threat; and emerging infectious diseases pose a continuing threat to the world. Given the perspectives gained and lessons learnt from these past events, we should be better prepared to face the current COVID-19 outbreak.
Topics: Betacoronavirus; COVID-19; China; Coronavirus Infections; Disease Outbreaks; Health Personnel; History, 21st Century; Humans; Occupational Diseases; Occupational Health; Pandemics; Pneumonia, Viral; SARS-CoV-2; Severe Acute Respiratory Syndrome; World Health Organization
PubMed: 32515882
DOI: 10.1002/1348-9585.12128 -
Journal of Vascular Surgery Dec 2022
Topics: Humans; Plaque, Atherosclerotic
PubMed: 36410846
DOI: 10.1016/j.jvs.2022.07.186 -
The Behavioral and Brain Sciences Nov 2023I strongly support Barzykowski and Moulin in their proposal that common retrieval mechanisms can lead to distinct phenomenological memory experiences. I emphasize the...
I strongly support Barzykowski and Moulin in their proposal that common retrieval mechanisms can lead to distinct phenomenological memory experiences. I emphasize the importance of one of these mechanisms, namely the attribution system. Neuropsychological studies should help clarifying the role of these retrieval mechanisms, notably in cases of medial temporal-lobe lesions and cases of dementia.
Topics: Humans; Memory, Episodic
PubMed: 37961781
DOI: 10.1017/S0140525X23000249