scholarly journals Cross-species anxiety tests in psychiatry: pitfalls and promises

2021 ◽  
Author(s):  
Dominik R. Bach
Keyword(s):  
Drug Screening ◽  
Healthy Human ◽  
Anxiolytic Drug ◽  
Healthy Humans ◽  
Potential Efficacy ◽  
The Social ◽  
Development Pipeline ◽  
Threat Avoidance ◽  
New Evidence ◽  
Independent Confirmation

AbstractBehavioural anxiety tests in non-human animals are used for anxiolytic drug discovery, and to investigate the neurobiology of threat avoidance. Over the past decade, several of them were translated to humans with three clinically relevant goals: to assess potential efficacy of candidate treatments in healthy humans; to develop diagnostic tests or biomarkers; and to elucidate the pathophysiology of anxiety disorders. In this review, we scrutinise these promises and compare seven anxiety tests that are validated across species: five approach-avoidance conflict tests, unpredictable shock anticipation, and the social intrusion test in children. Regarding the first goal, three tests appear suitable for anxiolytic drug screening in humans. However, they have not become part of the drug development pipeline and achieving this may require independent confirmation of predictive validity and cost-effectiveness. Secondly, two tests have shown potential to measure clinically relevant individual differences, but their psychometric properties, predictive value, and clinical applicability need to be clarified. Finally, cross-species research has not yet revealed new evidence that the physiology of healthy human behaviour in anxiety tests relates to the physiology of anxiety symptoms in patients. To summarise, cross-species anxiety tests could be rendered useful for drug screening and for development of diagnostic instruments. Using these tests for aetiology research in healthy humans or animals needs to be queried and may turn out to be unrealistic.

scholarly journals Sarcoglycan complex in masseter and sternocleidomastoid muscles of baboons: an immunohistochemical study

2015 ◽  
Vol 59 (2) ◽  
Author(s):  
G. Cutroneo ◽  
A. Centofanti ◽  
F. Speciale ◽  
G. Rizzo ◽  
A. Favaloro ◽  
...  
Keyword(s):  
Skeletal Muscles ◽  
Immunohistochemical Study ◽  
Epigenetic Modification ◽  
Expression Profiles ◽  
Muscle Fibres ◽  
Social Ranking ◽  
Healthy Humans ◽  
The Social ◽  
Almost All ◽  
Contractile Forces

<p>The sarcoglycan complex consists of a group of single-pass transmembrane glycoproteins that are essential to maintain the integrity of muscle membranes. Any mutation in each sarcoglycan gene causes a series of recessive autosomal dystrophin-positive muscular dystrophies. Negative fibres for sarcoglycans have never been found in healthy humans and animals. In this study, we have investigated whether the social ranking has an influence on the expression of sarcoglycans in the skeletal muscles of healthy baboons. Biopsies of masseter and sternocleidomastoid muscles were processed for confocal immunohistochemical detection of sarcoglycans. Our findings showed that baboons from different social rankings exhibited different sarcoglycan expression profiles. While in dominant baboons almost all muscles were stained for sarcoglycans, only 55% of muscle fibres showed a significant staining. This different expression pattern is likely to be due to the living conditions of these primates. Sarcoglycans which play a key role in muscle activity by controlling contractile forces may influence the phenotype of muscle fibres, thus determining an adaptation to functional conditions. We hypothesize that this intraspecies variation reflects an epigenetic modification of the muscular protein network that allows baboons to adapt progressively to a different social status.</p>

Absence of systematic relationships between REMS duration episodes and spectral power Delta and Ultra-Slow bands in contiguous NREMS episodes in healthy humans

2013 ◽  
Vol 110 (1) ◽  
pp. 162-169 ◽  
Author(s):  
O. Le Bon ◽  
P. Linkowski
Keyword(s):  
Spectral Power ◽  
Sleep Cycle ◽  
Consecutive Series ◽  
Sleep Regulation ◽  
Healthy Human ◽  
Sleep Quantity ◽  
Healthy Humans ◽  
Crucial Component ◽  
Sleep Physiology ◽  
Human Participants

Previous studies in animals and humans have reported correlations between the durations of rapid eye movement sleep (REMS) episodes and immediately preceding or subsequent non-REMS (NREMS) episodes. The relationship between these two types of sleep is a crucial component in understanding the regulation and neurophysiology of ultradian alternations that occur during sleep. Although the present study replicated previous studies, we also measured NREMS in terms of spectral power Delta and Ultra-Slow bands in addition to duration in examining correlations. The spectral power Delta band, also known as slow-wave activity, measures sleep quantity and is believed to reflect sleep physiology better than mere episode durations. The Ultra-Slow spectral power band was analyzed in parallel. Healthy human participants of both sexes ( n = 26, age range 15–45 yr, n = 12 female) were carefully selected to participate in two consecutive series of home polysomnograms performed after 2 nights of habituation to the equipment. In the analyses, REMS episode durations (minutes) were compared with immediately preceding and immediately subsequent NREMS episodes (Delta and Ultra-Slow power) in each sleep cycle. REMS episode duration was more strongly correlated with preceding NREMS episodes than with subsequent NREMS episodes. However, in most cases, no correlations were observed in either direction. One ultradian sleep regulation hypothesis, which is based on stronger correlations between REMS and subsequent NREMS episode durations, holds that the main purpose of REMS is to reactivate NREMS during each sleep cycle. The present results do not support that hypothesis.

scholarly journals Genotypic and Phenotypic Traits That Distinguish Neonatal Meningitis-Associated Escherichia coli from Fecal E. coli Isolates of Healthy Human Hosts

2012 ◽  
Vol 78 (16) ◽  
pp. 5824-5830 ◽  
Author(s):  
Catherine M. Logue ◽  
Curt Doetkott ◽  
Paul Mangiamele ◽  
Yvonne M. Wannemuehler ◽  
Timothy J. Johnson ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Phylogenetic Group ◽  
Neonatal Meningitis ◽  
Phenotypic Traits ◽  
Healthy Human ◽  
Content Type ◽  
Plasmid Content ◽  
E Coli ◽  
Healthy Humans ◽  
Definition Of

ABSTRACTNeonatal meningitisEscherichia coli(NMEC) is one of the top causes of neonatal meningitis worldwide. Here, 85 NMEC and 204 fecalE. coliisolates from healthy humans (HFEC) were compared for possession of traits related to virulence, antimicrobial resistance, and plasmid content. This comparison was done to identify traits that typify NMEC and distinguish it from commensal strains to refine the definition of the NMEC subpathotype, identify traits that might contribute to NMEC pathogenesis, and facilitate choices of NMEC strains for future study. A large number ofE. colistrains from both groups were untypeable, with the most common serogroups occurring among NMEC being O18, followed by O83, O7, O12, and O1. NMEC strains were more likely than HFEC strains to be assigned to the B2 phylogenetic group. Few NMEC or HFEC strains were resistant to antimicrobials. Genes that best discriminated between NMEC and HFEC strains and that were present in more than 50% of NMEC isolates were mainly from extraintestinal pathogenicE. coligenomic and plasmid pathogenicity islands. Several of these defining traits had not previously been associated with NMEC pathogenesis, are of unknown function, and are plasmid located. Several genes that had been previously associated with NMEC virulence did not dominate among the NMEC isolates. These data suggest that there is much about NMEC virulence that is unknown and that there are pitfalls to studying single NMEC isolates to represent the entire subpathotype.

scholarly journals Capsule Formulation of Ethanolic Extract of Pasak Bumi (Eurycoma Longifolia Jack.,) and its Effect on Human Health Vital Signs

2017 ◽  
Vol 22 (2) ◽  
pp. 91
Author(s):  
Laela Hayu Nurani ◽  
Eka Kumalasari ◽  
Abdul Rohman ◽  
Sitarina Widyarini
Keyword(s):  
Bitter Taste ◽  
Vital Signs ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Inclusion Criteria ◽  
Capsule Formulation ◽  
Healthy Human ◽  
Eurycoma Longifolia ◽  
Healthy Humans ◽  
Eurycoma Longifolia Jack

Pasak bumi (Eurycoma longifolia) has the potential to be developed as antihypertensive, antipyretic, aphrodisiacs and health supplements. The use of E. longifolia as a traditional medicine needs to be pursued in the form of more effective and appropriate formulation. The capsule preparations are easy to make and cancover the bitter taste of E. longifolia. Clinical trials in this study use design pre-post treatment in healthy humans. Subjects used were male - healthy men and healthy women who met inclusion criteria and were subjected with formulated capsule for 14 days. The study resulted capsule formula comprising of the ethanolic extract of E. longifolia 300 mg, vivapur 101 300 mg, 58 mg maydis starch, aerosil 3%, talc 2%, and Mg stearate 1%. The results showed that the capsule of E. longifolia did not affect the value of heart rate, respiration rate, body temperature and weight (P > 0.05), based on paired t-test, but they causes a decrease in blood pressure of healthy human. The ethanol extract of E. longifolia caused vasodilation of blood vessels that can be used in antihypertensive therapy.

Bracelets and Torcs

2021 ◽  
pp. 115-161
Author(s):  
Ellen Swift ◽  
Jo Stoner ◽  
April Pudsey
Keyword(s):  
Literature Review ◽  
Social Identities ◽  
Seventh Century ◽  
Late Antique ◽  
Social Functions ◽  
Data Set ◽  
Preliminary Discussion ◽  
The Social ◽  
New Evidence ◽  
Infants And Young Children

The chapter illuminates how bracelets and torcs were used to construct social identities, and their importance as protective artefacts, using new evidence, particularly relating to diameter sizes, to question some previous interpretations of these artefacts. It starts with a preliminary discussion regarding identification and how these objects were worn. The data set of bracelets is then presented and evidence for dating of particular bracelet types is considered. Evidence for the use and social function of bracelets is then set out, particularly diameter sizes, which are shown to be important in identifying use by people at particular life course stages, for instance infants and children. Bracelets are shown to be especially common as a children’s item in Egypt, in contrast to other provinces. One particular type of bracelet, the amuletic disc bracelet, is shown to be associated with protection during pregnancy. The chapter then examines torcs, and following a literature review and discussion of dating evidence for particular types, it is established that most are of sixth- to seventh-century CE date. It is also shown that, contrary to established opinion, torcs do not have military associations in the late antique period, at least in Egypt. The diameter sizes of types of non-openable torcs instead show a strong bias to wear by infants and young children. The social functions of torcs are then discussed, which could include protection, status assertion, and signifier of dedication to a particular role. Other topics discussed include inheritance of these objects within families.

Selective effects of serotonergic psychoactive agents on gastrointestinal functions in health

2003 ◽  
Vol 284 (1) ◽  
pp. G130-G137 ◽  
Author(s):  
Heather J. Chial ◽  
Michael Camilleri ◽  
Duane Burton ◽  
George Thomforde ◽  
Kevin W. Olden ◽  
...  
Keyword(s):  
Reuptake Inhibitor ◽  
Human Subjects ◽  
Functional Gastrointestinal Disorders ◽  
Gastric Volume ◽  
Colonic Transit ◽  
Selective Serotonin ◽  
Healthy Human ◽  
Double Blind ◽  
Solid Meal ◽  
Healthy Humans

This study evaluated the effects of serotonergic psychoactive agents on gastrointestinal functions in healthy human subjects. Participants received one of four regimens in a randomized, double-blind manner: buspirone, a 5-HT1Areceptor agonist (10 mg twice daily); paroxetine, a selective serotonin reuptake inhibitor (20 mg daily); venlafaxine-XR, a selective serotonin and norepinephrine reuptake inhibitor (75 mg daily); or placebo for 11 days. Physiological testing performed on days 8–11included scintigraphic assessment of gastrointestinal and colonic transit, the nutrient drink test, and assessment of the postprandial change in gastric volume. Fifty-one healthy adults (40 females, 11 males) participated in this study. No effects on gastric emptying or colonic transit were identified with any agent. Small bowel transit of a solid meal was accelerated by paroxetine. Buspirone decreased postprandial aggregate symptom and nausea scores. Venlafaxine-XR increased the postprandial change in gastric volume. Buspirone, paroxetine, and venlafaxine-XR affect upper gastrointestinal functions in healthy humans. These data support the need for clinical and physiological studies of these agents in functional gastrointestinal disorders.

scholarly journals Can the new epidemiology of schizophrenia help elucidate its causation?

2014 ◽  
Vol 31 (1) ◽  
pp. 1-5 ◽  
Author(s):  
R. T. Abed ◽  
M. J. Abbas
Keyword(s):  
Social Psychology ◽  
Clinical Trials ◽  
Life Time ◽  
Social Conditions ◽  
Low Risk ◽  
Social Brain ◽  
Ethnic Density ◽  
Increased Risk ◽  
The Social ◽  
New Evidence

The supposed universality of the incidence and prevalence of schizophrenia has been seriously challenged. It is now widely accepted that the life-time prevalence and incidence of this disorder vary considerably in time and place. As a result, there has been renewed interest in environmental causation of schizophrenia. There are few extant formulations that have successfully integrated the available new evidence into a coherent theory for its causation. The outgroup intolerance hypothesis is an attempt to integrate this evidence. It proposes that schizophrenia is the result of a mismatch between the social brain as shaped by evolution and the new social conditions of the post-neolithic. The hypothesis can provide an explanation for (i) the higher risk to migrants, (ii) the ethnic density phenomenon, (iii) the increased risk to individuals who have grown up in cities and (iv) the putative low risk in hunter-gatherer societies. Evidence is presented from a range of disciplines and sources including epidemiology, psychopathology, social psychology and clinical trials in support of this hypothesis. A range of testable predictions follow from the hypothesis.

Tankards of the British Iron Age

2015 ◽  
Vol 81 ◽  
pp. 311-341 ◽  
Author(s):  
Jonathan A. Horn
Keyword(s):  
Material Culture ◽  
Iron Age ◽  
Copper Alloy ◽  
Alloy Sheet ◽  
Manufacturing Processes ◽  
Roman Britain ◽  
Systematic Analysis ◽  
The Social ◽  
New Evidence

Iron Age tankards are stave-built wooden vessels completely covered or bound in copper-alloy sheet. The distinctive copper-alloy handles of these vessels frequently display intricate ‘Celtic’ or La Tène art styles. They are characterised by their often highly original designs, complex manufacturing processes, and variety of find contexts. No systematic analysis of this artefact class has been undertaken since Corcoran’s (1952a) original study was published in Volume 18 of these Proceedings. New evidence from the Portable Antiquities Scheme for England and Wales and recent excavations have more than quadrupled the number of known examples (139 currently). It is therefore necessary and timely to re-examine tankards, and to reintegrate them into current debates surrounding material culture in later prehistory. Tankards originate in the later Iron Age and their use continued throughout much of the Roman period. As such, their design was subject to varying influences over time, both social and aesthetic. Their often highly individual form and decoration is testament to this fact and has created challenges in developing a workable typology (Corcoran 1952a; 1952b; 1957; Spratling 1972; Jackson 1990). A full examination of the decoration, construction, wear and repair, dating, and deposition contexts will allow for a reassessment of the role of tankards within the social and cultural milieu of later prehistoric and early Roman Britain.

scholarly journals Efficacy and Safety of AVP-21D9, an Anthrax Monoclonal Antibody, in Animal Models and Humans

2014 ◽  
Vol 58 (7) ◽  
pp. 3618-3625 ◽  
Author(s):  
Nina V. Malkevich ◽  
Robert J. Hopkins ◽  
Edward Bernton ◽  
Gabriel T. Meister ◽  
Eric M. Vela ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Animal Models ◽  
Half Life ◽  
Healthy Human ◽  
Serious Adverse Events ◽  
Maximum Serum ◽  
Content Type ◽  
Elimination Half Life ◽  
Healthy Humans ◽  
Elimination Half

ABSTRACTAnthrax is an acute infectious disease caused by the spore-forming bacteriumBacillus anthracis. Timely administration of antibiotics approved for the treatment of anthrax disease may prevent associated morbidity and mortality. However, any delay in initiating antimicrobial therapy may result in increased mortality, as inhalational anthrax progresses rapidly to the toxemic phase of disease. An anthrax antitoxin, AVP-21D9, also known as Thravixa (fully human anthrax monoclonal antibody), is being developed as a therapeutic agent against anthrax toxemia. The efficacy of AVP-21D9 inB. anthracis-infected New Zealand White rabbits and in cynomolgus macaques was evaluated, and its safety and pharmacokinetics were assessed in healthy human volunteers. The estimated mean elimination half-life values of AVP-21D9 in surviving anthrax-challenged rabbits and nonhuman primates (NHPs) ranged from approximately 2 to 4 days and 6 to 11 days, respectively. In healthy humans, the mean elimination half-life was in the range of 20 to 27 days. Dose proportionality was observed for the maximum serum concentration (Cmax) of AVP-21D9 and the area under the concentration-time curve (AUC). In therapeutic efficacy animal models, treatment with AVP-21D9 resulted in survival of up to 92% of the rabbits and up to 67% of the macaques. Single infusions of AVP-21D9 were well tolerated in healthy adult volunteers across all doses evaluated, and no serious adverse events were reported. (This study has been registered at ClinicalTrials.gov under registration no. NCT01202695.)

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