There are increasing reports about stress related cognitive and psychic declines in subjects who have no psychiatric premorbidity, depression, or major life trauma. Yet, little is known about the ...underlying neurobiology. Based on the typical symptomatology, fMRI data suggesting that stress activates the limbic circuits, and animal data showing a major involvement of the 5-HT1A receptor in stress regulation, we hypothesized that enduring daily stress causes widespread limbic dysfunctions, and specific changes of the 5-HT1A receptor.
To test these hypotheses combined PET studies were carried out in 16 chronically stressed, and 16 non-stressed subjects. Limbic function was tested by measuring cerebral blood flow during rest, and when using an odor activation paradigm. 5-HT1A receptor binding potential (BP) was assessed with 11CWAY100635. All subjects went through a battery of neuropsychological tests.
Stressed subjects showed a functional disconnection between the amygdala and ACC/medial prefrontal cortex (mPFC), and an impaired odor activation of the ACC. They also displayed a reduced 5-HT1A receptor BP in the anterior cingulate (ACC), the insular-cortex, and the hippocampus. Their performance in attention-, odor discrimination-, and semantic memory tasks was impaired, and correlated with the BP-values in the respective region. The degree of reported stress was inversely correlated with activation of ACC, and the 5-HT1A receptor BP in the amygdala and hippocampus.
Enduring every day psychosocial stress seems to be associated with a limbic reduction of 5-HT1A receptor binding and functional disintegration of ACC/mPFC. These changes support the notion of an impaired top-down regulation of stress stimuli, and identify potential targets for early treatment.
► Chronic psychosocial stress is associated with disintegration of limbic networks. ► Stress patients display functional disconnection between amygdala and ACC/mPFC. ► Patients show limbic reductions of the 5-HT1A receptor binding. ► The degree of reported stress inversely correlates with ACC activation. ► The detected changes suggest a long-standing limbic malfunction.
Molecular radiotherapy combines the advantages of systemic administration of highly specific antibodies or peptides and the localized potency of ionizing radiation. A potential target for molecular ...radiotherapy is the cell surface antigen CD44v6, which is overexpressed in numerous cancers, with limited expression in normal tissues. The aim of the present study was to generate and characterize a panel of human anti-CD44v6 antibodies and identify a suitable candidate for future use in molecular radiotherapy of CD44v6-expressing cancers. Binders were first isolated from large synthetic phage display libraries containing human scFv and Fab antibody fragments. The antibodies were extensively analyzed through in vitro investigations of binding kinetics, affinity, off-target binding, and cell binding. Lead candidates were further subjected to in vivo biodistribution studies in mice bearing anaplastic thyroid cancer xenografts that express high levels of CD44v6. Additionally, antigen-dependent tumor uptake of the lead candidate was verified in additional xenograft models with varying levels of target expression. Interestingly, although only small differences were observed among the top antibody candidates in vitro, significant differences in tumor uptake and retention were uncovered in in vivo experiments. A high-affinity anti-CD44v6 lead drug candidate was identified, mAb UU-40, which exhibited favorable target binding properties and in vivo distribution. In conclusion, a panel of human anti-CD44v6 antibodies was successfully generated and characterized in this study. Through comprehensive evaluation, mAb UU-40 was identified as a promising lead candidate for future molecular radiotherapy of CD44v6-expressing cancers due to its high affinity, excellent target binding properties, and desirable in vivo distribution characteristics.
One working hypothesis behind transsexuality is that the normal sex differentiation of certain hypothalamic networks is altered. We tested this hypothesis by investigating the pattern of cerebral ...activation in 12 nonhomosexual male-to-female transsexuals (MFTRs) when smelling 4,16-androstadien-3-one (AND) and estra-1,3,5(10),16-tetraen-3-ol (EST). These steroids are reported to activate the hypothalamic networks in a sex-differentiated way. Like in female controls the hypothalamus in MFTRs activated with AND, whereas smelling of EST engaged the amygdala and piriform cortex. Male controls, on the other hand, activated the hypothalamus with EST. However, when restricting the volume of interest to the hypothalamus activation was detected in MFTR also with EST, and explorative conjunctional analysis revealed that MFTR shared a hypothalamic cluster with women when smelling AND, and with men when smelling EST. Because the EST effect was limited, MFTR differed significantly only from male controls, and only for EST-AIR and EST-AND. These data suggest a pattern of activation away from the biological sex, occupying an intermediate position with predominantly female-like features. Because our MFTRs were nonhomosexual, the results are unlikely to be an effect of sexual practice. Instead, the data implicate that transsexuality may be associated with sex-atypical physiological responses in specific hypothalamic circuits, possibly as a consequence of a variant neuronal differentiation.
Destruction and fragmentation of natural habitats results in small species populations that face increased risk of extinction. A time delay may be involved in the regional extinction of species, and ...the number of species that eventually may go extinct in the future is called the "extinction debt." In boreal Sweden, we examined whether the number of epiphytic crustose lichens and wood-inhabiting fungi in old-growth forest remnants diverges from species richness levels in forest patches that have been naturally isolated for millennia. An excess of species in forest remnants could indicate the presence of an extinction debt. Observed species richness in 32 old-growth forest remnants (also called woodland key habitats WKHs) was compared with predicted species richness. To predict species richness we used regression models based on data from 46 isolated old-growth forest patches in a forest-wetland matrix. The reference landscape is ancient and assumed to reflect the conditions of insular floras in dynamic equilibrium. Stand factors constituted predictive variables in the models. The observed number of lichen species was higher than expected (i.e., an extinction debt among lichens may exist). By contrast, there was no significant difference between observed and expected species richness among wood-inhabiting fungi. The species richness of wood-inhabiting fungi has adjusted to the changes in forest and landscape structure more rapidly than the species richness of lichens. Differences in substrate dynamics between epiphytes on living trees and species growing on decaying logs might explain the difference between species groups. The results also indicate that population densities of red-listed species were low, which may result in continuing extinctions of red-listed species. The importance of WKHs might be overvalued because species may be lost if conservation efforts consider only protection and preservation of WKHs.
Summary
The clinical examination in diagnostic criteria for temporomandibular disorders (DC/TMD) is a strict procedure and comprises mandatory commands. However, learning and using these mandatory ...commands in general practice have proven to be difficult and their use of DC/TMD is minimal. To investigate whether reliability on a diagnostic level for DC/TMD diagnoses differs between examiners using the mandatory commands or not. Six examiners were divided into two groups: one using the mandatory commands in DC/TMD for the clinical examination and one who did not use the mandatory commands. A reliability assessment was performed twice, one occasion for each group of examiners. The assessment was performed according to the guidelines from the International Network for Orofacial Pain and Related Disorders Methodology. Each group of examiners thereby examined 16 subjects (11 TMD patients and 5 healthy individuals) each, and the diagnostic agreement (reliability) as compared to diagnoses derived by a reference standard examiner was calculated with Cohen’ s kappa coefficient. The DC/TMD diagnoses myalgia, arthralgia and headache attributed to TMD were included in the reliability assessment. There was no significant difference regarding diagnostic agreement reliability between the examiners using or not using the mandatory DC/TMD commands. This study indicates that not using the mandatory commands in DC/TMD in general practice does not impair the diagnostic reliability regarding the diagnoses myalgia, arthralgia and headache attributed to TMD compared to including the commands.
The aim of this study was to evaluate the 1-year effect of the health-promoting intervention "senior meetings" for older community-dwelling persons regarding loneliness, social network, and social ...support.
Secondary analysis of data was carried out from two randomized controlled studies: Elderly Persons in the Risk Zone and Promoting Aging Migrants' Capabilities. Data from 416 participants who attended the senior meetings and the control group at baseline and the 1-year follow-up in the respective studies were included. Data were aggregated and analyzed with chi-square test and odds ratio (OR) to determine the intervention effect.
The senior meetings had a positive effect on social support regarding someone to turn to when in need of advice and backing (OR 1.72,
=0.01). No positive intervention effect could be identified for loneliness, social network, or other aspects of social support.
Health-promoting senior meetings for older community-dwelling persons have a minor positive effect on social support. The senior meetings might benefit from a revision to reinforce content focused on loneliness, social network, and social support. However, the modest effect could also depend on the lack of accessible social resources to meet participants' identified needs, a possible hindrance for a person's capability. This makes it necessary to conduct further research to evaluate the effect of the senior meetings and other health-promoting initiatives on social aspects of older community-dwelling people's lives, since these aspects are of high importance for life satisfaction and well-being in old age.
The effects of extracts from five cultivars of strawberries on the proliferation of colon cancer cells HT29 and breast cancer cells MCF-7 were investigated, and possible correlations with the levels ...of several antioxidants were analyzed. In addition, the effects of organic cultivation compared to conventional cultivation on the content of antioxidants in the strawberries and strawberry extracts on the cancer cell proliferation were investigated. The ratio of ascorbate to dehydroascorbate was significantly higher in the organically cultivated strawberries. The strawberry extracts decreased the proliferation of both HT29 cells and MCF-7 cells in a dose-dependent way. The inhibitory effect for the highest concentration of the extracts was in the range of 41−63% (average 53%) inhibition compared to controls for the HT29 cells and 26−56% (average 43%) for MCF-7 cells. The extracts from organically grown strawberries had a higher antiproliferative activity for both cell types at the highest concentration than the conventionally grown, and this might indicate a higher content of secondary metabolites with anticarcinogenic properties in the organically grown strawberries. For HT29 cells, there was a negative correlation at the highest extract concentration between the content of ascorbate or vitamin C and cancer cell proliferation, whereas for MCF-7 cells, a high ratio of ascorbate to dehydroascorbate correlated with a higher inhibition of cell proliferation at the second highest concentration. The significance of the effect of ascorbate on cancer cell proliferation might lie in a synergistic action with other compounds. Keywords: Ascorbate; dehydroascorbate; phenolics; hydroxycinnamic acids; ellagic acid; flavonol; anthocyanin; cancer cell proliferation; correlation
► CWD volume remained high throughout natural fire succession in boreal spruce forests. ► Species richness and CWD volume had a strong but non-linear relationship. ► Low amount of CWD and ...impoverished polypore diversity characterized clear-cut forests. ► A threshold value of 18m3ha−1 was detected for the occurrence of red-listed species.
We tested the extent to which forestry mimics natural stand-replacing fire dynamics, and what factors best explain species richness and assemblages of polyporous fungi in natural northern boreal Picea abies-dominated forests and managed forests which were either clear-cut and planted with pine, or selectively logged. The amount of coarse woody debris (CWD) and diversity of polypores in old-growth forests and in forests at three natural post-fire successional stages (young, middle-aged, old) were compared with managed forests at comparable successional stages. Fire created a high amount of CWD, providing a supply of dead wood for saproxylic species for at least 50–70y. Dead wood volumes remained high throughout the natural forest succession, exceeding at all stages 18m3ha−1, the threshold value established in the study for the occurrence of red-listed species. The richness of polypore species was highest on young post-fire sites, and their species composition, including red-listed species, was comparable to that of old-growth forests (>300y) used as references. The amount of CWD in natural post-fire forests was over two to twenty times higher than that on clear-cut sites, and species diversity on clear-cut sites was considerably lower than on sites undergoing natural succession, with no occurrences of red-listed species. A relatively diverse polypore flora was found in selectively logged forests, likely due to rather a high volume and continuity of spruce CWD. The results indicate a strong but non-linear relationship between total volume of CWD and species richness of polypores, but successional stage and naturalness also explained part of the variation. The species assemblages were influenced most by the decay stage of CWD, tree species composition and naturalness of the site. The results demonstrate the importance of old-growth and young post-fire forests as landscape-level habitats and species pools, especially for red-listed species. We recommend that old-growth spruce forests be preserved whenever possible and that high CWD volumes be generated locally for red-listed species, for example, by prescribed burning. Regeneration forests for spruce, extended rotation periods and the use of logging techniques other than clear-cutting would help in maintaining species diversity in spruce-associated species in boreal forests.
The preparation and capacity of doctoral students to become stewards of the discipline by their contribution to research literature are critically important for the future of social work. The present ...study examined the publication and impact of social work dissertation research to assess whether and how dissertation research contributes to the body of knowledge. A random sample of 593 social work dissertation abstracts from dissertations published in ProQuest Dissertations and Abstracts between 1998 and 2008 from US member schools of the Group for the Advancement of Doctoral Education (GADE) comprised the sample for this study. Searches in Google Scholar were conducted to locate published empirical peer-reviewed articles or books published from dissertation research. Citation counts were extracted and impact values (Impact Factor, h- and g-index) were utilised to examine dissertation impact. Findings indicate that a small proportion (28.8 per cent) of social work dissertations were published. Those published seem to enter into the discourse of the social work discipline and other disciplinary fields as evidenced by publication in many higher-impact journals across disciplines. The overall lack of dissertation research being published suggests a significant failure of social work doctoral education. Implications and recommendations for the field are discussed.
Differential scanning fluorimetry (DSF) is a rapid and inexpensive screening method to identify low-molecular-weight ligands that bind and stabilize purified proteins. The temperature at which a ...protein unfolds is measured by an increase in the fluorescence of a dye with affinity for hydrophobic parts of the protein, which are exposed as the protein unfolds. A simple fitting procedure allows quick calculation of the transition midpoint; the difference in the temperature of this midpoint in the presence and absence of ligand is related to the binding affinity of the small molecule, which can be a low-molecular-weight compound, a peptide or a nucleic acid. DSF is best performed using a conventional real-time PCR instrument. Ligand solutions from a storage plate are added to a solution of protein and dye, distributed into the wells of the PCR plate and fluorescence intensity measured as the temperature is raised gradually. Results can be obtained in a single day.
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