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Memory modification technology (MMT) refers to the use of neurotechnologies to intervene in memory. Some scholars oppose the application of MMT in mental health therapy because MMT undermines personal autonomy. Such judgment is based on several different reasons: (1) MMT is an inactive intervention; (2) MMT sacrifices long-term autonomy; (3) MMT promotes paternalism; (4) MMT leads users to relinquish their social relationships. This article argues that due to the philosophical complexities of the concept of autonomy, current debates have been unable to provide a valid justification for the ethical permissibility of MMT. In fact, the autonomy-based arguments against MMT focus on conceptual aspects of autonomy other than informed consent. A focus on informed consent may be of greater moral significance. We should adopt a more practical perspective of personal autonomy and focus on the informed consent issues in MMT. [ABSTRACT FROM AUTHOR]

Background Anxiety disorders are highly prevalent and socio-economically costly. Novel pharmacological treatments for these disorders are needed because many patients do not respond to current agents or experience unwanted side effects. However, a barrier to treatment development is the variable and large placebo response rate seen in trials of novel anxiolytics. Despite this, the mechanisms that drive placebo responses in anxiety disorders have been little investigated, possibly due to low availability of convenient experimental paradigms. We aimed to develop and test a novel protocol for inducing placebo anxiolysis in the 7.5% CO2 inhalational model of generalized anxiety in healthy volunteers. Methods Following a baseline 20-minute CO2 challenge, 32 healthy volunteers were administered a placebo intranasal spray labelled as either the anxiolytic "lorazepam" or "saline." Following this, participants surreptitiously underwent a 20-minute inhalation of normal air. Post-conditioning, a second dose of the placebo was administered, after which participants completed another CO2 challenge. Results Participants administered sham "lorazepam" reported significant positive expectations of reduced anxiety (P  = .001), but there was no group-level placebo effect on anxiety following CO2 challenge post-conditioning (P s > .350). Surprisingly, we found many participants exhibited unexpected worsening of anxiety, despite positive expectations. Conclusions Contrary to our hypothesis, our novel paradigm did not induce a placebo response, on average. It is possible that effects of 7.5% CO2 inhalation on prefrontal cortex function or behavior in line with a Bayesian predictive coding framework attenuated the effect of expectations on subsequent placebo response. Future studies are needed to explore these possibilities. [ABSTRACT FROM AUTHOR]

The inclusion of women psychologists in arenas of academic and professional recognition has been a slow and often invisible process. This study seeks to highlight the scientific contributions of six women psychologists classified as eminent during the twentieth century (Haggbloom et al., Review of General Psychology, 6(2), 139–152, 2002) and the contexts in which they developed. Applying a historiographic and bibliometric approach, we analyzed biographical data and scientific contributions by reviewing the Web of Science, Scopus and APA PsycNet databases. The results show the broad contributions of the six psychologists to the field of psychology in the areas of experimental psychology, childhood and memory. We discuss the importance of rendering visible and overcoming the epistemic injustices to which women in psychology are subject, as well as the resistance and strategies many of them used to confront the structural limitations of this environment. [ABSTRACT FROM AUTHOR]

The poison dart toxin batrachotoxin is exceptional for its high potency and toxicity, and for its multifaceted modification of the function of voltage-gated sodium channels. By using cryogenic electron microscopy, we identify two homologous, but nonidentical receptor sites that simultaneously bind two molecules of toxin, one at the interface between Domains I and IV, and the other at the interface between Domains III and IV of the cardiac sodium channel. Together, these two bound toxin molecules stabilize α/π helical conformation in the S6 segments that gate the pore, and one of the bound BTX-B molecules interacts with the crucial Lys1421 residue that is essential for sodium conductance and selectivity via an apparent water-bridged hydrogen bond. Overall, our structure provides insight into batrachotoxin’s potency, efficacy, and multifaceted functional effects on voltage-gated sodium channels via a dual receptor site mechanism.The poison dart toxin batrachotoxin is the most lethal voltage-gated sodium channel toxin. Here authors identify the toxin bound specifically at two homologous receptor sites, which cause channel hyperactivation by positively modulating channel gating and altering ion conductance. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder; the prevalence of which has been on the rise with unknown causes. Alterations in the gut-brain axis have been widely recognized in ASD patients, and probiotics are considered to potentially benefit the rescuing of autism-like behaviors. However, the effectiveness and mechanisms of multiple probiotics on zebrafish models are still not clearly revealed. This study aims to use the germ-free (GF) and conventionally raised (CR) AB wild-type zebrafish and the mutant Tbr1b -/- and Katnal2 -/- lines as human-linked ASD animal models to evaluate the effects of multiple probiotics on mitigating developmental and behavioral defects. Results showed that the addition of probiotics increased the basic important developmental indexes, such as body length, weight, and survival rate of treated zebrafish. Moreover, the Lactobacillus plantarum and Lactobacillus rhamnosus affected the behavior of CR zebrafish by increasing their mobility, lowering the GF zebrafish manic, and mitigating transgenic zebrafish abnormal behavior. Moreover, the expression levels of key genes related to gamma-aminobutyric acid (GABA), dopamine (DA), and serotonin (5-HT) as important neuropathways to influence the appearance and development of autism-related disorders, including gad1b, tph1a, htr3a, th, and slc6a3, were significantly activated by some of the probiotics' treatment at some extent. Taken together, this study indicates the beneficial effects of different probiotics, which may provide a novel understanding of probiotic function in related diseases' therapy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A bearded vulture (Gypaetus barbatus) found dead in northern Spain presented external lesions consistent with electrocution as the cause of death. During forensic examination, macroscopic lesions suggested potential comorbidity, so samples were collected for molecular and toxicological analyses. Gastric content and liver were analysed for toxic substances, and pentobarbital (a common pharmaceutical used for euthanasia in domestic animals) was detected at a concentration of 37.3 and 0.05 µg/g, respectively. Other toxicological, viral and endoparasite analyses (avian malaria, avian influenza and flaviviruses) were negative. Thus, although the cause of death was electrocution, pentobarbital intoxication likely impaired the equilibrium and reflexes of the individual, possibly causing the bird to contact energized wires that it would not have otherwise. These results underline the importance of comprehensive analysis of forensic cases of wildlife deaths and reveal barbiturate poisoning as an additional threat for the conservation of the bearded vulture in Europe. [ABSTRACT FROM AUTHOR]

Background: Nicotine cessation leads to anxiety and depression. Aims: The suitability of the zebrafish model of anhedonia using reserpine and fluoxetine was evaluated. Fluoxetine was also used to reduce nicotine withdrawal-induced anhedonic state. Methods: Zebrafish were exposed to reserpine (40 mg/l) and then to fluoxetine (0.1 mg/l) for 1 week. Anhedonia was evaluated in the Novel Tank Diving and Compartment Preference tests. Another group was exposed to nicotine (1 mg/l/2 weeks) and then exposed to fluoxetine. Anxiety and anhedonia were evaluated 2–60 days after. Tyrosine hydroxylase (TH) immunoreactivity and microglial morphology (labelled by 4C4 monoclonal antibody) in the parvocellular pretectal nucleus (PPN), dorsal part, and of calcitonin gene-related peptide (CGRP) in the hypothalamus were also analysed. Results: Less time in the top and increased latency to the top in reserpine compared to a drug-free group was found. Fluoxetine rescued reserpine-induced the reduced time in the top. Seven and 30 days after nicotine withdrawal more time in the bottom and similar time in the Compartment Preference test, rescued by fluoxetine, were shown. In the PPN, 30-day withdrawal induced an increase in TH immunoreactivity, but fluoxetine induced a further significant increase. No changes in PPN microglia morphology and hypothalamic CGRP were detected. Conclusions: Our findings validate the suitability of the zebrafish model of anhedonia using the reserpine-induced depression-like behaviour and the predictivity using fluoxetine. Fluoxetine rescued nicotine withdrawal-induced anhedonic state, opening the possibility to screen new drugs to alleviate anxiety and depression in smokers during abstinence. [ABSTRACT FROM AUTHOR]

Amphibians are one of the most remarkable sources of unique natural products. Biogenic amines, peptides, bufodienolides, alkaloids, and volatile organic compounds have been characterized in different species. The superfamily Dendrobatoidea represents one of the most enigmatic cases of study in chemical ecology because their skin secretome is composed by a complex mixture (i.e. cocktail) of highly lethal and noxious unique alkaloid structures. While chemical defences from dendrobatoids (families Dendrobatidae and Aromobatidae) have been investigated employing ecological, behavioral, phylogenetic and evolutionary perspectives, studies about the analytical techniques needed to perform the chemical characterization have been neglected for many years. Therefore, our aim is to summarize the current methods applied for the characterization of chemical profiles in dendrobatoids and to illustrate innovative Eco-metabolomics strategies that could be translated to this study model. This approach could be extended to natural products other than alkaloids and implemented for the chemical analysis of different species of dendrobatoids employing both low- and high-resolution mass spectrometers. Here, we overview important biological features to be considered, procedures that could be applied to perform the chemical characterization, steps and tools to perform an Eco-metabolomic analysis, and a final discussion about future perspectives. [ABSTRACT FROM AUTHOR]

From pre-historic era, all scientific discoveries have evolved around a concept – THINK BIG but for a change zebrafish as a model organism in research had managed to halt the entire medical community and made us realize that it's time to think small. From a barely imagined being in research few years ago to around 4,000 publications in just last year, zebrafish has definitely come a long way. Through these tiny fish, scientists have managed to find genes that caused human diseases and have also developed various specific models to know more about the pathology behind such diseases. This review will focus on zebrafish as a model organism from the time it was introduced to the most novel targets with particular emphasis on central nervous system (CNS) as it is rapidly evolving branch in zebrafish research these days. This review will try to shed light on the early stages of zebrafish as a model organism and will try to cover the journey of it developing as a successful model organism to map many diseases like diabetes, Alzheimer's and autism describing the rationale for using this specific model and briefly the techniques under each category and finally will summarize the pros and cons of the model with its expected future directions. [ABSTRACT FROM AUTHOR]

Tobacco smoking imposes a staggering burden on public health, underscoring the urgency of developing a deeper understanding of the processes that maintain addiction. Clinical and experience-sampling data highlight the importance of anxious withdrawal symptoms, but the underlying neurobiology has remained elusive. Mechanistic work in animals implicates the central extended amygdala (EAc)—including the central nucleus of the amygdala and the neighboring bed nucleus of the stria terminalis—but the translational relevance of these discoveries remains unexplored. Here we leveraged a randomized trial design, well-established threat-anticipation paradigm, and multidimensional battery of assessments to understand the consequences of 24-hour nicotine abstinence. The threat-anticipation paradigm had the expected consequences, amplifying subjective distress and arousal, and recruiting the canonical threat-anticipation network. Abstinence increased smoking urges and withdrawal symptoms, and potentiated threat-evoked distress, but had negligible consequences for EAc threat reactivity, raising questions about the translational relevance of prominent animal and human models of addiction. These observations provide a framework for conceptualizing nicotine abstinence and withdrawal, with implications for basic, translational, and clinical science. [ABSTRACT FROM AUTHOR]

Background: Pain is the primary reason people seek medical care, with chronic pain affecting ~ 20% of people in the USA. However, many existing analgesics are ineffective in treating chronic pain, while others (e.g., opioids) have undesirable side effects. Here, we describe the screening of a small molecule library using a thermal place aversion assay in larval zebrafish to identify compounds that alter aversion to noxious thermal stimuli and could thus serve as potential analgesics. Results: From our behavioral screen, we discovered a small molecule, Analgesic Screen 1 (AS1), which surprisingly elicited attraction to noxious painful heat. When we further explored the effects of this compound using other behavioral place preference assays, we found that AS1 was similarly able to reverse the negative hedonic valence of other painful (chemical) and non-painful (dark) aversive stimuli without being inherently rewarding. Interestingly, targeting molecular pathways canonically associated with analgesia did not replicate the effects of AS1. A neuronal imaging assay revealed that clusters of dopaminergic neurons, as well as forebrain regions located in the teleost equivalent of the basal ganglia, were highly upregulated in the specific context of AS1 and aversive heat. Through a combination of behavioral assays and pharmacological manipulation of dopamine circuitry, we determined that AS1 acts via D1 dopamine receptor pathways to elicit this attraction to noxious stimuli. Conclusions: Together, our results suggest that AS1 relieves an aversion-imposed "brake" on dopamine release, and that this unique mechanism may provide valuable insight into the development of new valence-targeting analgesic drugs, as well as medications for other valence-related neurological conditions, such as anxiety and post-traumatic stress disorder (PTSD). [ABSTRACT FROM AUTHOR]

Uchi-komi exercises are the most important component of judo training. This study aimed to investigate the effect of different rest intervals during high-intensity intermittent uchi-komi exercises on total technique repetitions and physiological load in judo athletes. Twenty-two male judo athletes (mean age 19.0 ± 1.2 years, judo experience 7.6 ± 22.7 years) voluntarily participated in this study. Athletes' body composition and judo-specific performance were determined. The athletes randomly performed 20 seconds × 8 sets of high-intensity intermittent exercise using ippon-seoi-nage technique with 1:1/2, 1:1, 1:2, and 1:3 work-to-rest ratios on separate days. Before and 1, 7, 15, and 30 minutes after each exercise, athletes' heart rate (HR) and blood lactate were determined. The number of repetitions differed according to rest durations, when the rest duration decreased, the number of the repetitions decreased (F21, 441 = 7.09, p < 0.001). Blood lactate responses were similar during the exercises with different rest intervals (F3,63 = 2.15, p = 0.10). The shorter the rest duration, the higher the HR (F3,63 = 6.81, p < 0.001). The current study proposed that 1:2 and 1:3 work-to-rest ratios at high-intensity intermittent uchi-komi exercise are the most appropriate intervals to ensure a high number of technique repetitions and the continuity of the training. [ABSTRACT FROM AUTHOR]

Copyright of Revista de la Facultad de Medicina de la UNAM is the property of UNAM, Facultad de Medicina and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In the present work, 224 adult female zebrafish (56 fish in each group) were randomly divided into four groups (two control groups and two toxicity groups) as per duration of exposure (7 and 21 days). All fish of the two toxicity groups were exposed to 0.610 mM acrylamide (ACR) concentration for 7 and 21 days. The effects of ACR exposure on behavior, oxidative stress biomarkers, molecular expression of antioxidant genes (sod, cat, and nrf2), and histopathological examination of the brain and eye were examined. Our result shows that ACR exposure for 7 days produced an anxiety-like behavior in zebrafish. Short-term exposure of ACR resulted in alterations of oxidative stress markers (SOD and CAT activity, and the level of GSH and MDA) in the brain and eye of zebrafish. However, the antioxidant defense system of adult female zebrafish could be able to counteract the free radicals generated in long-term ACR exposure as indicated by non-significant difference in oxidative insult following short-term and long-term exposure. ACR exposure downregulated the mRNA expression of the sod, cat, and nrf2 (nuclear factor erythroid 2–related factor 2) genes in the brain and eye without significant difference between the two toxicity groups. Mild histological changes in the dorsal telencephalic area, tectum opticum, medulla, and hypothalamus area of the brain of zebrafish have been observed following short-term and long-term ACR exposure. In the eye, marked histological changes in the retinal pigmented epithelium layer (RPE), structural changes of the photoreceptor layer (PRL) with disorganized layer of rods and cones, and reduction of the relative thickness of the RPE, PRL, outer nuclear layer (ONL), and inner nuclear layer (INL) have been noted following ACR exposure for 21 days as compared to 7 days. ACR produced neurobehavioral aberrations and oxidative stress within 7 days of exposure, while various histological changes in the brain and eyes have been observed following long-term exposure (21 days) to ACR. [ABSTRACT FROM AUTHOR]

The European Commission asked EFSA for a scientific opinion on the risks for human health of the presence of grayanotoxins (GTXs) in 'certain honey' from Ericaceae plants. The risk assessment included all structurally related grayananes occurring with GTXs in 'certain' honey. Oral exposure is associated with acute intoxication in humans. Acute symptoms affect the muscles, nervous and cardiovascular systems. These may lead to complete atrioventricular block, convulsions, mental confusion, agitation, syncope and respiratory depression. For acute effects, the CONTAM Panel derived a reference point (RP) of 15.3 μg/kg body weight for the sum of GTX I and III based on a BMDL10 for reduced heart rate in rats. A similar relative potency was considered for GTX I. Without chronic toxicity studies, an RP for long‐term effects could not be derived. There is evidence for genotoxicity in mice exposed to GTX III or honey containing GTX I and III, showing increased levels of chromosomal damage. The mechanism of genotoxicity is unknown. Without representative occurrence data for the sum of GTX I and III and consumption data from Ericaceae honey, acute dietary exposure was estimated based on selected concentrations for GTX I and III reflecting concentrations measured in 'certain' honeys. Applying a margin of exposure (MOE) approach, the estimated MOEs raised health concerns for acute toxicity. The Panel calculated the highest concentrations for GTX I and III below which no acute effects would be expected following 'certain honey' consumption. The Panel is 75% or more certain that the calculated highest concentration of 0.05 mg for the sum of GTX I and III per kg honey is protective for all age groups regarding acute intoxications. This value does not consider other grayananes in 'certain honey' and does not cover the identified genotoxicity. [ABSTRACT FROM AUTHOR]

Background Altered redox state and developmental abnormalities in glutamatergic and GABAergic transmission during development are linked to the behavioral changes associated with schizophrenia. As an amino acid that exerts antioxidant and inhibitory actions in the brain, taurine is a potential candidate to modulate biological targets relevant to this disorder. Here, we investigated in mice and zebrafish assays whether taurine prevents the behavioral changes induced by acute administration of MK-801 (dizocilpine), a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist. Methods C57BL/6 mice were i.p. administered with saline or taurine (50, 100, and 200 mg/kg) followed by MK-801 (0.15 mg/kg). Locomotor activity, social interaction, and prepulse inhibition of the acoustic startle reflex were then assessed in different sets of animals. Zebrafish were exposed to tank water or taurine (42, 150, and 400 mg/L) followed by MK-801 (5 µM); social preference and locomotor activity were evaluated in the same test. Results MK-801 induced hyperlocomotion and disrupted sensorimotor gating in mice; in zebrafish, it reduced sociability and increased locomotion. Taurine was mostly devoid of effects and did not counteract NMDA antagonism in mice or zebrafish. Discussion Contradicting previous clinical and preclinical data, taurine did not show antipsychotic-like effects in the present study. However, it still warrants consideration as a preventive intervention in animal models relevant to the prodromal phase of schizophrenia; further studies are thus necessary to evaluate whether and how taurine might benefit patients. [ABSTRACT FROM AUTHOR]

Opioid receptors are widely expressed in the brain, and the opioid system has a key role in modulating mood, reward processing and stress responsivity. There is mounting evidence that the endogenous opioid system may be dysregulated in depression and that drug treatments targeting mu, delta and kappa opioid receptors may show antidepressant potential. The mechanisms underlying the therapeutic effects of opioid system engagement are complex and likely multi-factorial. This chapter explores various pathways through which the modulation of the opioid system may influence depression. These include impacts on monoaminergic systems, the regulation of stress and the hypothalamic-pituitary-adrenal axis, the immune system and inflammation, brain-derived neurotrophic factors, neurogenesis and neuroplasticity, social pain and social reward, as well as expectancy and placebo effects. A greater understanding of the diverse mechanisms through which opioid system modulation may improve depressive symptoms could ultimately aid in the development of safe and effective alternative treatments for individuals with difficult-to-treat depression., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Irving Janis's concept of 'groupthink', the idea that a collective desire for consensus overrides the realistic appraisals of alternatives and leads to poor group decision making, is a staple of social science textbooks. Despite gaining little support in empirical studies, Janis's eight symptoms of groupthink remains a popular framework. What has been forgotten, however, is that nearly 20 years before Janis's supposed invention, groupthink was coined by social critic William H Whyte, author of one of the 1950s, most influential books on management. Adding to the growing interest in a historical turn in Management and Organization Studies, we investigate how and why Whyte's groupthink was over-written by a history that found Janis's ideas more useful, and outline how recovering Whyte can add value to our thinking now. [ABSTRACT FROM AUTHOR]

Xanthohumol (Xn) is a chalcone compound isolated from Humulus lupulus Linn., that has various biological activities. In this study, eight Xn derivatives were synthesized by Williamson, Mannich, Reimer-Tiemann, and Schiff base reactions, and evaluated for their in vitro cytotoxic activity against five human cancer cell lines (MDA-MB-231, MCF-7, CNE-2Z, SMMC-7721, and H1975). Among these compounds, 2-((E)-2,4-dihydroxy-5-((E)-3-(4-hydroxyphenyl)acryloyl)-6-methoxy-3-(3- methylbut-2-en-1-yl)benzylidene)hydrazine-1-carboximidamide (8) exhibited the most potent cytotoxic activity against the five cancer cells, with IC 50 values ranging from 4.87 to 14.35 µM. Wound-healing and transwell assays showed that compound 8 inhibited the migration and invasion of MDA-MB-231 cells by down-regulation HIF-1α, MMP-2 and MMP-9 protein expression. We further demonstrated that compound 8 induced apoptosis of MDA-MB-231 cells by increasing of Bax/Bcl-2 ratio and down-regulation of Akt protein expression., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In this systematic review, we highlight the differences between the male and female zebrafish brains to understand their differentiation and their use in studying sex-specific neurological diseases. Male and female brains display subtle differences at the cellular level which may be important in driving sex-specific signaling. Sex differences in the brain have been observed in humans as well as in non-human species. However, the molecular mechanisms of brain sex differentiation remain unclear. The classical model of brain sex differentiation suggests that the steroid hormones derived from the gonads are the primary determinants in establishing male and female neural networks. Recent studies indicate that the developing brain shows sex-specific differences in gene expression prior to gonadal hormone action. Hence, genetic differences may also be responsible for differentiating the brain into male and female types. Understanding the signaling mechanisms involved in brain sex differentiation could help further elucidate the sex-specific incidences of certain neurological diseases. The zebrafish model could be appropriate for enhancing our understanding of brain sex differentiation and the signaling involved in neurological diseases. Zebrafish brains show sex-specific differences at the hormonal level, and recent advances in RNA sequencing have highlighted critical sex-specific differences at the transcript level. The differences are also evident at the cellular and metabolite levels, which could be important in organizing sex-specific neuronal signaling. Furthermore, in addition to having one ortholog for 70% of the human gene, zebrafish also shares brain structural similarities with other higher eukaryotes, including mammals. Hence, deciphering brain sex differentiation in zebrafish will help further enhance the diagnostic and pharmacological intervention of neurological diseases. [ABSTRACT FROM AUTHOR]

Mood disorders, especially depression, are a major cause of human disability. The loss of pleasure (anhedonia) is a common, severely debilitating symptom of clinical depression. Experimental animal models are widely used to better understand depression pathogenesis and to develop novel antidepressant therapies. In rodents, various experimental models of anhedonia have already been developed and extensively validated. Complementing rodent studies, the zebrafish (Danio rerio) is emerging as a powerful model organism to assess pathobiological mechanisms of affective disorders, including depression. Here, we critically discuss the potential of zebrafish for modeling anhedonia and studying its molecular mechanisms and translational implications. [ABSTRACT FROM AUTHOR]

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Working memory (WM) abilities are frequently impaired in neurological disorders affecting fronto-parietal cortical/sub-cortical structures. WM deficits negatively influence interventional outcomes and everyday functioning. This study thus aimed at the following: (a) developing and standardizing an ecologically valid task for WM assessment (Ice Cream Test, ICT); (b) validating and norming a novel WM test (Digit Ordering Test, DOT), as well as providing updated norms for digit span (DS) tasks, in an Italian population sample; (c) introducing a novel scoring procedure for measuring WM. Methods: One-hundred and sixty-eight Italian healthy participants—73 male, 95 females; age: 48.4 ± 19.1 (18–86); education: 12.1 ± 4.8 (4–21)—underwent a thorough WM assessment—DOT, ICT, and both forward and backward DS tasks (FDS, BDS). The ICT requires participants to act as waiters who have to keep track of customers' orders. For each task, WM and total (T) outcomes were computed, i.e., the number of elements in the longest sequence and that of recalled sequences, respectively. Norms were derived via the equivalent score (ES) method. Results: DS ratios (DSRs) were computed for both WM/S and T outcomes on raw DS measures (BDS divided by FDS). Age and education significantly predicted all WM tasks; sex affected FDS and DSR-T scores (males > females). WM measures were highly internally related. Discussion: The present work provides Italian practitioners with a normatively updated, multi-component, adaptive battery for WM assessment (WoMAB) as well as with novel outcomes which capture different WM facets—WM capacity and attentive monitoring abilities. [ABSTRACT FROM AUTHOR]

Hops (Humulus lupulus L.) are known worldwide for their application in the food industry by providing both aroma and flavor to the beer. Considering its popularity as an indispensable brewing crop, a lot of information can be found in the literature about the bioactive compounds present in hop cones. However, current research pointed that hop application can go further than brewing. The present review updates the emerging technologies used to extract hop bioactive compounds in comparison with the conventional ones. The main characteristics, extraction conditions, and extracted compounds of these environmentally friendly extraction methods are highlighted, helping to understand their importance and industrial applications, especially considering hop phytochemicals and their potential for the food industry. In addition, considering this still little addressed potential, this work summarizes the use of hops in different food matrices and emphasizes the relevant aspects that circumvent it. The development of "hopped products" in addition to their potential use as food preservatives expanded the hop industrial perspectives. Among the non-beer foods, meat products, minimally processed vegetables, bread, and premium products, including non-alcoholic beverages, showed up as great options to hop compound incorporation. Consumer perception based on current trends for hopped products also indicates interesting prospects for industrial spread. [ABSTRACT FROM AUTHOR]

Data from the past 30+ years of the male boxing World Heavyweight Championship (n = 182 bouts) was obtained. The USA were the most represented and produced more champions than any other nation, followed by the UK, Ukraine and Russia. Denmark (100%), Ukraine (85.4%) and the UK (67.3%) produced the greatest 'success rates' in World Heavyweight Championship contests. Where possible, comparisons between bout winners and losers were also made. Winners were significantly taller (p < 0.001, d = 0.35) and had a greater reach (p = 0.003, d = 0.23) when compared to losers. Championship bouts were settled by the following methods: a form of knockout (101), points decision (57), retirement (14), draw (3), disqualification (3), technical decision (1), whilst 3 no contests were omitted from the analysis. Total punches thrown and landed, and jabs and power punches thrown and landed were consistently significantly greater (p < 0.005, d = 0.27–0.73) in winners, compared to losers. Winners were more accurate compared to their losing counterparts by ~ 8 percentage points. The data presented in the present study clearly show some anthropometric advantages of championship bout winners, compared to their unsuccessful counterparts, and that winners are more active and accurate when compared to losers. The punch output data, albeit very basic, may be useful in informing tactical strategy and preparation of heavyweight prospects. Likewise, the data in the present study may be an interesting resource for professional boxing enthusiasts. Future research should seek to replicate the analysis in the present study across other weight divisions to explore any potential differences between weight classes. Additionally, extending the analysis to female boxing may provide interesting comparisons. [ABSTRACT FROM AUTHOR]

To the SLC6 family belong 20 human transporters that utilize the sodium electrochemical gradient to move biogenic amines, osmolytes, amino acids and related compounds into cells. They are classified into two functional groups, the Neurotransmitter transporters (NTT) and Nutrient amino acid transporters (NAT). Here we summarize how since their first cloning in 1998, the insect (Lepidopteran) Orthologs of the SLC6 family transporters have represented very important tools for investigating functional–structural relationships, mechanism of transport, ion and pH dependence and substate interaction of the mammalian (and human) counterparts. [ABSTRACT FROM AUTHOR]

Rationale: Triazole 1.1 is a novel kappa-opioid receptor (KOR) agonist reported to produce antinociception without KOR-typical adverse effects. When combined with the mu-opioid receptor (MOR) agonist, oxycodone, triazole 1.1 blocks oxycodone-induced pruritis without producing sedation-like effects in nonhuman primates. However, it is unknown if triazole 1.1 can reduce the abuse-related effects or enhance the antinociceptive effects of oxycodone similarly to other KOR agonists. Objectives: The aim of the present study was to quantitatively compare the behavioral effects of triazole 1.1 to the KOR agonists, U50,488h and nalfurafine, on oxycodone self-administration and oxycodone-induced thermal antinociception when administered as mixtures with oxycodone. Methods: In the self-administration study, male Sprague–Dawley (SD) rats (n = 6) self-administered intravenous (i.v.) oxycodone alone (0.056 mg/kg/inj) or combined with U50,488 h (0.032-0.32 mg/kg/inj), nalfurafine (0.00032–0.0032 mg/kg/inj), or triazole 1.1 (0.32–1.8 mg/kg/inj) under a progressive-ratio schedule of reinforcement. In a hot plate assay, male SD rats (n = 6) received i.v. injections of oxycodone (1.0-5.6 mg/kg), U50,488h (1.0-18.0 mg/kg), nalfurafine (0.01-1.0 mg/kg), or triazole 1.1 (3.2-32.0 mg/kg) alone or in combinations of fixed proportion with oxycodone based on the relative potencies of the single drugs. Each study concluded with administration of the KOR antagonist nor-BNI and some degree of retesting of the previous conditions to verify that the behavioral effects were mediated by KOR activation. Results: All KOR agonists reduced oxycodone self-administration in a dose-dependent manner. Moreover, all single drugs and drug combinations produced dose-dependent, fully efficacious thermal antinociception. All KOR agonist:oxycodone combinations produced either additive or super-additive thermal antinociception. Finally, each KOR agonist was blocked in effect by nor-BNI in both behavioral measures. Conclusion: This study demonstrates that triazole 1.1 reduces oxycodone's reinforcing effects and enhances oxycodone-induced antinociception to degrees that are comparable to typical KOR agonists. Given triazole 1.1's mild adverse-effect profile, developing MOR-KOR agonist combinations from the triazole 1.1 series may render new pain therapeutics with reduced abuse liability. [ABSTRACT FROM AUTHOR]

Standardization and reduction of variation is key to behavioural screening of animal models in toxicological and pharmacological studies. However, individual variation in behavioural and physiological phenotypes remains in each laboratory population and can undermine the understanding of toxicological and pharmaceutical effects and their underlying mechanisms. Here, we used zebrafish (ABTL-strain) larvae to explore individual consistency in activity level and emergence time, across subsequent days of early development (6–8 dpf). We also explored the correlation between these two behavioural parameters. We found inter-individual consistency over time in activity level and emergence time, but we did not find a consistent correlation between these parameters. Subsequently, we investigated the impact of variation in activity level on the effect of a 1% ethanol treatment, suitable for our proof-of-concept case study about whether impact from pharmacological treatments might be affected by inter-individual variation in basal locomotion. The inter-individual consistency over time in activity level did not persist in this test. This was due to the velocity change from before to after exposure, which turned out to be a dynamic individual trait related to basal activity level: low-activity individuals raised their swimming velocity, while high-activity individuals slowed down, yielding diametrically opposite response patterns to ethanol exposure. We therefore argue that inter-individual consistency in basal activity level, already from 6 dpf, is an important factor to take into account and provides a practical measure to improve the power of statistical analyses and the scope for data interpretation from behavioural screening studies. [ABSTRACT FROM AUTHOR]

A broad spectrum of chemical entities have been associated with drug-induced seizure (DIS), emphasizing the importance of this potential liability across various drug classes (e.g., antidepressants, antipsychotics, antibiotics, and analgesics among others). Despite its importance within drug safety testing, an understanding of the molecular mechanisms associated with DIS is often lacking. The etiology of DIS is understood to be a result of either a deficit in inhibitory (e.g., gamma aminobutyric acid) or an elevated excitatory (e.g., glutamate) signaling, leading to synchronous neuronal depolarization affecting various brain regions and impairing normal neurological functions. How this altered neuronal signaling occurs and how these changes interact with other non-brain receptor driven DIS-associated changes such as metabolic disturbances, electrolyte imbalances, altered drug metabolism, and withdrawal effects are poorly understood. Herein, we discuss important molecular mechanisms identified in DIS for several drugs and/or drug classes. With a better understanding of the molecular mechanisms associated with DIS, in vivo or in vitro models may be applied to characterize and mitigate DIS risk during drug development. Susceptibility stratification for DIS presents species differences in the following order beagle dogs > rodents and cynomolgus monkeys > Göttingen minipigs with a more than 2-fold difference between canines and minipigs, which is important to consider during non-clinical species selection. While clinical signs such as myoclonus, severe muscle jerks, or convulsions are often associated with abnormal epileptiform EEG activity, tremors are most of the time physiological and rarely observed with concurrent epileptiform EEG activity which need to be considered during DIS risk evaluation. [ABSTRACT FROM AUTHOR]

We owe him the duty of carrying on the upward progress, and Professor Michael Rutter will be greatly missed. He laid the groundwork for the development of fields of child psychiatry and developmental psychopathology.[[1]] His appointment as professor of child psychiatry in the United Kingdom was historic since he was the first one of his kind. Dear Editor, Sir Michael Llewellyn Rutter CBE FRS FRCP FRCPsych FMedSci (Aug 15, 1933-Oct 23, 2021) was a British psychiatrist who was widely considered as the "father of modern child psychiatry". [Extracted from the article]

Animal studies are recognized as a significant step forward in the bridging between drug discovery and clinical applications. Animal models, due to their relative genetic, molecular, physiological, and even anatomical similarities to humans, can provide a suitable platform for unraveling the mechanisms underlying human diseases and discovering new therapeutic approaches as well. Recently, zebrafish has attracted attention as a valuable experimental and pharmacological model in drug discovery and development studies due to its prominent characteristics such as the high degree of genetic similarity with humans, genetic manipulability, and prominent clinical features. Since advancing a theory to a valid and reliable observation requires the manipulation of animals, it is, therefore, essential to use efficient modeling methods appropriate to the different aspects of experimental conditions. In this context, applying several various approaches such as using chemicals, pathogens, and genetic manipulation approaches allows zebrafish development into a preferable model that mimics some human disease pathophysiology. Thus, such modeling approaches not only can provide a framework for a comprehensive understanding of the human disease mechanisms that have a counterpart in zebrafish but also can pave the way for discovering new drugs that are accompanied by higher amelioration effects on different human diseases., (© 2021. Springer Nature Switzerland AG.)

The kappa opioid receptor (KOR), a G protein-coupled receptor, and its endogenous ligands, the dynorphins, are prominent members of the opioid neuromodulatory system. The endogenous kappa opioid system is expressed in the central and peripheral nervous systems, and has a key role in modulating pain in central and peripheral neuronal circuits and a wide array of physiological functions and neuropsychiatric behaviors (e.g., stress, reward, emotion, motivation, cognition, epileptic seizures, itch, and diuresis). We review the latest advances in pharmacology of the KOR, chemical developments on KOR ligands with advances and challenges, and therapeutic and potential applications of KOR ligands. Diverse discovery strategies of KOR ligands targeting natural, naturally derived, and synthetic compounds with different scaffolds, as small molecules or peptides, with short or long-acting pharmacokinetics, and central or peripheral site of action, are discussed. These research efforts led to ligands with distinct pharmacological properties, as agonists, partial agonists, biased agonists, and antagonists. Differential modulation of KOR signaling represents a promising strategy for developing pharmacotherapies for several human diseases, either by activating (treatment of pain, pruritus, and epilepsy) or blocking (treatment of depression, anxiety, and addiction) the receptor. We focus on the recent chemical and pharmacological advances on diphenethylamines, a new class of structurally distinct, selective KOR ligands. Design strategies and investigations to define structure-activity relationships together with in vivo pharmacology of diphenethylamines as agonists, biased agonists, and antagonists and their potential use as therapeutics are discussed., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

From pre-historic era, all scientific discoveries have evolved around a concept - THINK BIG but for a change zebrafish as a model organism in research had managed to halt the entire medical community and made us realize that it's time to think small. From a barely imagined being in research few years ago to around 4,000 publications in just last year, zebrafish has definitely come a long way. Through these tiny fish, scientists have managed to find genes that caused human diseases and have also developed various specific models to know more about the pathology behind such diseases. This review will focus on zebrafish as a model organism from the time it was introduced to the most novel targets with particular emphasis on central nervous system (CNS) as it is rapidly evolving branch in zebrafish research these days. This review will try to shed light on the early stages of zebrafish as a model organism and will try to cover the journey of it developing as a successful model organism to map many diseases like diabetes, Alzheimer's and autism describing the rationale for using this specific model and briefly the techniques under each category and finally will summarize the pros and cons of the model with its expected future directions., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)