Introduction
Differences between women and men matter in the prevalence and risk factors of dementia. We aimed to examine potential sex differences regarding the effectiveness by running a secondary ...analysis of the AgeWell.de trial, a cluster-randomized multicenter multi-domain lifestyle intervention to reduce cognitive decline.
Methods
Intention-to-treat analyses of women (n=433) and men (n=386) aged 60 to 77 years were used for models including interactions between intervention group allocation and sex followed by subgroup analysis stratified by sex on primary and secondary outcomes. Further, the same procedure was repeated for age groups (60–69 vs. 70–77) within sex-specific subgroups to assess the effectiveness in different age groups. Trial registration: German Clinical Trials Register (ref. number: DRKS00013555).
Results
No differences were found between women and men in the effectiveness of the intervention on cognitive performance. However, women benefitted from the intervention regarding depressive symptoms while men did not. Health-related quality of life was enhanced for younger intervention participants (60–69 years) in both women and men.
Conclusion
The AgeWell.de intervention was able to improve depressive symptoms in women and health-related quality of life in younger participants. Female participants between 60 and 69 years benefited the most. Results support the need of better individually targeted lifestyle interventions for older adults.
The medicinal chemistry and preclinical biology of imidazopyridine-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) is described. A screening hit 1 with low lipophilic efficiency (LipE) ...was optimized through two key structural modifications: (1) identification of the pyrrolidine amide group for a significant LipE improvement, and (2) insertion of a sp3-hybridized carbon center in the core of the molecule for simultaneous improvement of N-glucuronidation metabolic liability and off-target pharmacology. The preclinical candidate 9 (PF-06424439) demonstrated excellent ADMET properties and decreased circulating and hepatic lipids when orally administered to dyslipidemic rodent models.
To examine patterns of blubber loss accompanying a decline in body condition, blubber thickness of juvenile harbor porpoises in normal/robust body condition (
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) was compared with that of starved conspecifics (
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). Blubber thickness in the thorax of starved porpoises (9–11 mm) was only 50%–60% of that of normal animals (18–20 mm); however, very little tailstock blubber was lost during starvation. Adipocytes in thorax and tailstock blubber were measured in both groups (
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) to determine whether thickness changes were homogeneous throughout blubber depth. In the thorax of normal porpoises, adipocytes near the epidermis (outer blubber) were smaller (0.11 nL) than inner blubber adipocytes (0.17 nL). Conversely, the size of tailstock adipocytes was uniform. Starved animals had fewer, smaller adipocytes in the inner thorax blubber, suggesting a possible combination of adipocyte shrinkage and loss. Lipids were withdrawn only from the inner layer of thorax blubber during starvation, supporting a hypothesis of regional specialization of function in blubber. Blubber of the thorax serves as the site of lipid deposition and mobilization, while the tailstock is metabolically inert and likely important in locomotion and streamlining. Therefore, some proportion of the blubber of small odontocetes must be considered structural/mechanical rather than an energy reserve.
Introduction
Three-dimensional collagen matrices (3D-CMs) may be visualized by cumbersome reconstructions of serial sections. We report here on the method of synchrotron-based X-ray tomographic ...microscopy (SRXTM) to image 3D-CMs in native tissue probes.
Material and methods
SRXTM of 3D-CMs (mucoderm®, mucograft®) was performed at the TOMCAT beamline of the Swiss Light Source (SLS) at the Paul Scherrer Institute (Villigen, Switzerland).
Results
SRXTM combines the advantages of high-resolution scanning electron microscopy (SEM) imaging with the low-resolution reconstructions of micro-CT (μCT) imaging. It may be used to non-destructively visualize and analyze structures within the 3D-CMs without the need of serial sectioning and reconstruction.
Conclusion
High-resolution SRXTM is a useful tool in analyzing the topology and morphometry of structures in 3D-CMs. The outcome justifies the efforts in sophisticated data processing.
Clinical relevance
SRXTM may help to understand the clinical characteristics of 3D-CMs in more detail.
How to theorise religion in International Relations (IR)? Does the concept of post-secularity advance the debate on religion beyond the ‘return of religion’ and the crisis of secular reason? This ...article argues that the post-secular remains trapped in the logic of secularism. First, a new account is provided of the ‘secularist bias’ that characterises mainstream IR theory: (a) defining religion in either essentialist or epiphenomenal terms; (b) positing a series of ‘antagonistic binary opposites’ such as the secular versus the religious; and (c) de-sacralising and re-sacralising the public square. The article then analyses post-secularity, showing that it subordinates faith under secular reason and sacralises the ‘other’ by elevating difference into the sole transcendental term. Theorists of the post-secular such as Jürgen Habermas or William Connolly also equate secular modernity with metaphysical universalism, which they seek to replace with post-metaphysical pluralism. In contrast, the alternative that this article outlines is an international theory that develops the Christian realism of the English School in the direction of a metaphysical-political realism. Such a realism binds together reason with faith and envisions a ‘corporate’ association of peoples and nations beyond the secularist settlement of Westphalia that is centred on national states and transnational markets. By linking immanent values to transcendent principles, this approach can rethink religion in international affairs and help revive grand theory in IR.
Abstract Acid challenge of the gastric mucosa is signaled to the brainstem. This study examined whether mild gastritis due to dextrane sulfate sodium (DSS) or iodoacetamide (IAA) enhances gastric ...acid–evoked input to the brainstem and whether this effect is related to gastric myeloperoxidase activity, gastric histology, gastric volume retention or cyclooxygenase stimulation. The stomach of conscious mice was challenged with NaCl (0.15 M) or HCl (0.15 and 0.25 M) administered via gastric gavage. Two hours later, activation of neurons in the nucleus tractus solitarii (NTS) was visualized by c-Fos immunocytochemistry. Gastritis was induced by DSS (molecular weight 8000; 5%) or IAA (0.1%) added to the drinking water for 7 days. Relative to NaCl, intragastric HCl increased the number of c-Fos protein-expressing cells in the NTS. Pretreatment with DSS or IAA for 1 week did not alter the c-Fos response to NaCl but significantly enhanced the response to HCl by 54 and 74%, respectively. Either pretreatment elevated gastric myeloperoxidase activity and induced histological injury of the mucosal surface. In addition, DSS caused dilation of the gastric glands and damage to the parietal cells. HCl-induced gastric volume retention was not altered by IAA but attenuated by DSS pretreatment. Indomethacin (5 mg/kg) failed to significantly alter HCl-evoked expression of c-Fos in the NTS of control, DSS-pretreated and IAA-pretreated mice. We conclude that the gastritis-evoked increase in the gastric acid-evoked c-Fos expression in the NTS is related to disruption of the gastric mucosal barrier, mucosal inflammation, mucosal acid influx and enhanced activation of the afferent stomach–NTS axis.
Background and purpose: Transient receptor potential ankyrin 1 (TRPA1) channels are expressed by primary afferent neurones and activated by irritant chemicals including allyl isothiocyanate (AITC). ...Here we investigated whether intracolonic AITC causes afferent input to the spinal cord and whether this response is modified by mild colitis, morphine or a TRPA1 channel blocker.
Experimental approach: One hour after intracolonic administration of AITC to female mice, afferent signalling was visualized by expression of c‐Fos in laminae I–IIo of the spinal dorsal horn at sacral segment S1. Mild colitis was induced by dextran sulphate sodium (DSS) added to drinking water for 1 week.
Key results: Relative to vehicle, AITC (2%) increased expression of c‐Fos in the spinal cord. Following induction of mild colitis by DSS (2%), spinal c‐Fos responses to AITC, but not vehicle, were augmented by 41%. Colonic inflammation was present (increased myeloperoxidase content and disease activity score), whereas colonic histology, locomotion, feeding and drinking remained unchanged. Morphine (10 mg·kg–1) or the TRPA1 channel blocker HC‐030031 (300 mg·kg–1) inhibited the spinal c‐Fos response to AITC, in control and DSS‐pretreated animals, whereas the response to intracolonic capsaicin (5%) was blocked by morphine but not HC‐030031.
Conclusions and implications: Activation of colonic TRPA1 channels is signalled to the spinal cord. Mild colitis enhanced this afferent input that, as it is sensitive to morphine, is most likely of a chemonociceptive nature. As several irritant chemicals can be present in chyme, TRPA1 channels may mediate several gastrointestinal pain conditions.
Abstract
The sister taxon of one of the most diverse and pharmacologically important heterobranch gastropod groups, Nudibranchia, is unclear. Pleurobranchomorpha have been recovered sister to ...Nudibranchia in most molecular phylogenetic studies to date, forming a clade called Nudipleura. However, this relationship has not been consistently recovered; some phylogenomic studies have recovered Nudipleura as a paraphyletic group, but transcriptome data have been available from only one representative of Pleurobranchomorpha to date. Here, we supplemented the paucity of data available for Pleurobranchomorpha by sequencing the transcriptome of Bathyberthella antarctica Willan & Bertsch, 1987 and analysing transcriptomes and genomes from a total of 27 gastropod species, inferring the phylogeny of Heterobranchia based on 993 genes. Consistent with analyses of datasets dominated by 18 S rDNA and recent phylogenomic studies, all of our analyses unequivocally support Nudipleura, recovering Nudibranchia as sister to Pleurobranchomorpha with maximal support. Our study supports previous hypotheses that nudipleurans evolved from a common ancestor with an androdiaulic reproductive system, a blood gland and a secondarily lost osphradium.
Buoyant balaenids: the ups and downs of buoyancy in right whales Nowacek, Douglas P.; Johnson, Mark P.; Tyack, Peter L. ...
Proceedings - Royal Society. Biological sciences/Proceedings - Royal Society. Biological Sciences,
09/2001, Letnik:
268, Številka:
1478
Journal Article
Recenzirano
Odprti dostop
A variety of marine mammal species have been shown to conserve energy by using negative buoyancy to power prolonged descent glides during dives. A new non-invasive tag attached to North Atlantic ...right whales recorded swim stroke from changes in pitch angle derived from a three-axis accelerometer. These results show that right whales are positively buoyant near the surface, a finding that has significant implications for both energetics and management. Some of the most powerful fluke strokes observed in tagged right whales occur as they counteract this buoyancy as they start a dive. By contrast, right whales use positive buoyancy to power glides during ascent. Right whales appear to use their positive buoyancy for more efficient swimming and diving. However, this buoyancy may pose added risks of vessel collision. Such collisions are the primary source of anthropogenic mortality for North Atlantic right whales, whose population is critically endangered and declining. Buoyancy may impede diving responses to oncoming vessels and right whales may have a reduced ability to manoeuvre during free ascents. These risk factors can inform efforts to avoid collisions.
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