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Differentiating anxiety from fear: An experimental-pharmacological approach
Grayâs theory of personality postulates that fear and anxiety are distinct emotional systems with only the latter being sensitive to anxiolytic drugs. His work was mainly based on animal research and translational studies validating his theory are scarce. Previous work in humans showed an influence of the benzodiazepine lorazepam on both systems, however, dependent on dosage (1 and 2mg) and personality differences in negative emotionality. The present study aims to replicate these findings, and in addition tests the drug threshold effect by introducing a lower dosage of 0.5mg lorazepam.
Fifty healthy adults (23 males, agemean 22.40, SD±3.68) participated in an experimental threat-avoidance paradigm designed to dissociate risk assessment intensity (RAI, reflecting anxiety) and flight intensity (FI, reflecting fear) and completed two self-report questionnaires assessing facets of negative emotionality (Spielberger Trait Anxiety Inventory and Fear Survey Schedule). In a randomized placebo-controlled within-subject design, 0.5mg and 1mg of lorazepam were applied per os. Saccadic peak velocity was assessed by means of eye-tracking in order to control for sedating drug effects.
Results showed the expected and specific anxiolytic effect of lorazepam on RAI, however only in the 0.5mg condition. FI was not influenced by lorazepam and previous findings of interaction effects of lorazepam with self-reported negative emotionality could not be corroborated.
Overall, this study demonstrates anxiolytic effects of lorazepam in dosages †1mg in the absence of a drug effect on fear using a translational behavioural task. However, a putative moderating role of personality on defensive behaviour has to be clarified in future research
Depression and anxiety screening identifies patients that may benefit from treatment regardless of existing diagnoses
BACKGROUND: This study investigated the utility of depression and anxiety symptom screening in patients scheduled for total knee arthroplasty to examine differences in active symptoms according to patients\u27 mental health diagnoses and associated prescription medications.
MATERIAL AND METHODS: This cross-sectional study analyzed 594 patients scheduled for total knee arthroplasty at a tertiary practice between June 2018 and December 2018. Patients completed Patient-Reported Outcomes Measurements Information System (PROMIS) Depression and Anxiety Computerized Adaptive Tests in clinic quantifying active symptoms. Mental health diagnoses and associated medications were extracted from health records. Statistical analysis assessed between-group differences in mean PROMIS scores and the prevalence of heightened depressive and anxiety symptoms.
RESULTS: Multivariable linear regression modeling demonstrated that being diagnosed with depression without medication (ÎČ 7.1;
CONCLUSION: One in seven arthroplasty patients screened reported heightened depressive and/or anxiety symptoms. Despite the majority of arthroplasty patients on antidepressants and anxiolytics having symptoms controlled, these patients remain at increased risk of heightened active symptoms
HumusqualitÀt und Bodenstruktur: Was kontrolliert die Lachgas-Emissionen aus landwirtschaftlich genutzten Böden?
In den letzten Jahrzehnten wurde der globale N-Kreislauf nicht nur durch die Verbrennung fossiler EnergietrĂ€ger, sondern auch durch Anwendung von DĂŒngemitteln drastisch verĂ€ndert. GefĂ€hrdung des Grundwassers und Beitrag zur globalen Klimaentwicklung sind bekannte Folgewirkungen. In Böden ist die Denitrifikation hauptverantwortlich fĂŒr die RĂŒckfĂŒhrung des Stickstoffs in die AtmosphĂ€re und gehört somit zu den SchlĂŒsselprozessen im N-Kreislauf. Obwohl lĂ€ngst bekannt ist, dass denitrifizierende Bodenorganismen hierfĂŒr organische Bodensubstanz (OBS) sowohl als C-Substrat als auch als Elektronendonator nutzen, ist hierbei die Rolle funktioneller OBS-Fraktionen (HumusqualitĂ€t) sowie deren rĂ€umliche und zeitliche VerfĂŒgbarkeit in unterschiedlichen AggregatgröĂenfraktionen weitestgehend unbekannt. Aus diesem Grund werden die Auswirkungen spezifischer funktioneller OBS-Fraktionen (gelöste und partikulĂ€re OBS) auf den Beginn und das AusmaĂ der Denitrifikation in definierten Inkubationsexperimenten untersucht. Insbesondere fĂŒr die N2O-Bildung durch Denitrifikation scheinen anoxische âMikrohabitateâ im Inneren der Aggregate relevant. Im Statischen DĂŒngeversuch in Bad LauchstĂ€dt untersuchen wir daher den Einfluss langfristiger DĂŒngeranwendungen (Applikation von N-, NP- und organischem DĂŒnger) auf die Akkumulation bestimmter funktioneller OBS-Fraktionen sowie auf die Aggregatstruktur und infolgedessen auf das Treibhausgasemissionspotential (neben N2O auch CO2 und CH4). Gasemissionsmessungen aus ungestörten Bodenproben sollen zeigen, inwieweit das DĂŒngungsmanagement ĂŒber die Kontrolle der HumusqualitĂ€t und/oder des Aggregationsstatus die Treibhausgasemissionen aus landwirtschaftlich genutzten Böden steuert
Glycoform analysis of intact erythropoietin by MALDI FT-ICR mass spectrometry
Recombinant human erythropoietin (EPO) is a complex therapeutic glycoprotein with three N- and one O-glycosylation sites. Glycosylation of EPO influences its safety and efficacy and is defined as a critical quality attribute. Thus, analytical methods for profiling EPO glycosylation are highly demanded. Owing to the complexity of the intact protein, information about EPO glycosylation is commonly derived from released glycan and glycopeptide analysis using mass spectrometry (MS). Alternatively, comprehensive insights into the glycoform heterogeneity of intact EPO are obtained using ESI MS-based methods with or without upfront separation of EPO glycoforms. MALDI MS, typically performed with TOF mass analyzers, has been also used for the analysis of intact EPO but, due to the poor glycoform resolution, has only provided limited glycoform information. Here, we present a MALDI FT-ICR MS method for the glycosylation profiling of intact EPO with improved glycoform resolution and without loss of sialic acid residues commonly observed in MALDI analysis. Three EPO variants were characterized in-depth and up to 199 glycoform compositions were assigned from the evaluation of doubly-charged ions, without any deconvolution of the mass spectra. Key glycosylation features such as sialylation, acetylation, and N- acetyllactosamine repeats were determined and found to agree with previously reported data obtained from orthogonal analyses. The developed method allowed for a fast and straightforward data acquisition and evaluation and can be potentially used for the high-throughput comparison of EPO samples throughout its manufacturing process. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Proteomic
Human paternal and maternal demographic histories: Insights from high-resolution Y chromosome and mtDNA sequences
BACKGROUND: Comparisons of maternally-inherited mitochondrial DNA (mtDNA) and paternally-inherited non-recombining Y chromosome (NRY) variation have provided important insights into the impact of sex-biased processes (such as migration, residence pattern, and so on) on human genetic variation. However, such comparisons have been limited by the different molecular methods typically used to assay mtDNA and NRY variation (for example, sequencing hypervariable segments of the control region for mtDNA vs. genotyping SNPs and/or STR loci for the NRY). Here, we report a simple capture array method to enrich Illumina sequencing libraries for approximately 500Â kb of NRY sequence, which we use to generate NRY sequences from 623 males from 51 populations in the CEPH Human Genome Diversity Panel (HGDP). We also obtained complete mtDNA genome sequences from the same individuals, allowing us to compare maternal and paternal histories free of any ascertainment bias. RESULTS: We identified 2,228 SNPs in the NRY sequences and 2,163 SNPs in the mtDNA sequences. Our results confirm the controversial assertion that genetic differences between human populations on a global scale are bigger for the NRY than for mtDNA, although the differences are not as large as previously suggested. More importantly, we find substantial regional variation in patterns of mtDNA versus NRY variation. Model-based simulations indicate very small ancestral effective population sizes (<100) for the out-of-Africa migration as well as for many human populations. We also find that the ratio of female effective population size to male effective population size (N(f)/N(m)) has been greater than one throughout the history of modern humans, and has recently increased due to faster growth in N(f) than N(m). CONCLUSIONS: The NRY and mtDNA sequences provide new insights into the paternal and maternal histories of human populations, and the methods we introduce here should be widely applicable for further such studies
Metabolomics demonstrates divergent responses of two Eucalyptus species to water stress
Past studies of water stress in Eucalyptus spp. generally highlighted the role of fewer than five âimportantâ metabolites, whereas recent metabolomic studies on other genera have shown tens of compounds are affected. There are currently no metabolite profiling data for responses of stress-tolerant species to water stress. We used GCâMS metabolite profiling to examine the response of leaf metabolites to a long (2 month) and severe (Κpredawn < â2 MPa) water stress in two species of the perennial tree genus Eucalyptus (the mesic Eucalyptus pauciflora and the semi-arid Eucalyptus dumosa). Polar metabolites in leaves were analysed by GCâMS and inorganic ions by capillary electrophoresis. Pressureâvolume curves and metabolite measurements showed that water stress led to more negative osmotic potential and increased total osmotically active solutes in leaves of both species. Water stress affected around 30â40% of measured metabolites in E. dumosa and 10â15% in E. pauciflora. There were many metabolites that were affected in E. dumosa but not E. pauciflora, and some that had opposite responses in the two species. For example, in E. dumosa there were increases in five acyclic sugar alcohols and four low-abundance carbohydrates that were unaffected by water stress in E. pauciflora. Re-watering increased osmotic potential and decreased total osmotically active solutes in E. pauciflora, whereas in E. dumosa re-watering led to further decreases in osmotic potential and increases in total osmotically active solutes. This experiment has added several extra dimensions to previous targeted analyses of water stress responses in Eucalyptus, and highlights that even species that are closely related (e.g. congeners) may respond differently to water stress and re-waterin
Scoliosis and dental occlusion: a review of the literature
<p>Abstract</p> <p>Background</p> <p>Idiopathic scoliosis is a deformity without clear etiology. It is unclear wether there is an association between malocclusion and scoliosis. Several types of occlusion were described in subjects with scoliosis, mostly case-reports.</p> <p>Objectives</p> <p>The aim of this review was to evaluate the type of occluslins more prevalent in subjects with scoliosis</p> <p>Search strategy</p> <p>All randomised and controlled clinical trials identified from the Cochrane Oral Health Group Trials Register, a MEDLINE search using the Mesh term scoliosis, malocclusion, and relevant free text words, and the bibliographies of papers and review articles which reported the outcome of orthodontic treatment in subjects with scoliosis that were published as abstracts or papers between 1970 and 2010.</p> <p>Selection criteria</p> <p>All randomised and controlled clinical trials published as full papers or abstracts which reported quantitative data on the outcomes malocclusion in subjects with scoliosis.</p> <p>Data collection and analysis</p> <p>Data were extracted without blinding to the authors, age of patients or type of occlusion.</p> <p>Main results</p> <p>Using the search strategy eleven observational longitudinal studies were identified. No randomized clinical trials were recorded. Twenty-three cross-sectional studies were recorderd, and the others studies were reviews, editorials, case-reports, or opinions. The clinical trials were often not controlled and were about the cephalometric evaluation after treatment with the modified Milwuakee brace, followed by the orthodontic treatment of the class II relationship with a functional appliance. Clinical trials also included the study of the associations between scoliosis and unilateral crossbite, in children with asymmetry of the upper cervical spine. This association was also investigated in rats, pigs and rabbits in clinical trials. The other associations between scoliosis and occlusion seems to be based only on cross-sectional studies, case-reports, opinions.</p> <p>Authors' conclusions</p> <p>Based on selected studies, this review concludes that there is plausible evidence for an increased prevalence of unilateral Angle Class II malocclusions associated with scoliosis, and an increased risk of lateral crossbite, midline deviation in children affected by scoliosis. Also, documentation of associations between reduced range of lateral movements and scoliosis seem convincing. Data are also mentioned about the association between plagiocephaly and scoliosis.</p
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