Association of Sleep Duration and Quality With Alterations in the Hypothalamic-Pituitary Adrenocortical Axis: The Multi-Ethnic Study of Atherosclerosis (MESA)

Context: Short sleep duration and poor sleep quality are associated with cardiovascular outcomes. One mechanism proposed to explain this association is altered diurnal cortisol secretion. Objective: The objective of the study was to examine the associations of sleep duration and sleep quality with diurnal salivary cortisol levels. Design: This was a cross-sectional analysis using data from examination 5 (2010–2012) of the Multi-Ethnic Study of Atherosclerosis. Actigraphy-based measures of sleep duration and efficiency were collected over 7 days, and salivary cortisol samples were collected over 2 days from participants aged 54–93 years (n = 600 with analyzable data). Results: Shorter average sleep duration (<6 h/night) was associated with less pronounced late decline in cortisol [2.2% difference in slope; 95% confidence interval (CI) 0.8–3.7; P ≤ .01] and less pronounced wake-to-bed slope (2.2% difference; 95% CI 1.0–3.4; P ≤ .001) compared with longer sleep duration (≥6 h/night). Lower sleep efficiency (<85%) was associated with less pronounced early decline in cortisol (29.0% difference in slope; 95% CI 4.1–59.7; P < .05) compared with higher sleep efficiency (≥85%). Subjects reporting insomnia had a flatter cortisol awakening response (−16.1% difference in slope; 95% CI −34.6 to −0.1; P < .05) compared with those not reporting insomnia. Conclusions: Shorter sleep duration, lower sleep efficiency, and insomnia are associated with alterations in diurnal cortisol levels consistent with changes in hypothalamic-pituitary-adrenal regulation

Omentum is highly effective in the management of complex cardiothoracic surgical problems

AbstractObjectives: Vascularized, pedicled tissue flaps are often used for cardiothoracic surgical problems complicated by factors that adversely affect healing, such as previous irradiation, established infection, or steroid use. We reviewed our experience with use of the omentum in these situations to provide a yardstick against which results with other vascularized flaps (specifically muscle flaps) could be compared. Methods: A retrospective review was undertaken of 85 consecutive patients in whom omentum was used in the chest. In 47 patients (group I), use of omentum was prophylactic to aid in the healing of closures or anastomoses considered to be at high risk for failure. In 32 patients (group II), omentum was used in the treatment of problems complicated by established infection. In 6 patients (group III), omentum was used for coverage of prosthetic chest wall replacements after extensive chest wall resection. Results: Overall, omental transposition was successful in its prophylactic or therapeutic purpose in 88% of these difficult cases (75/85). Success with omentum was achieved for 89% of patients (42/47) in group I, 91% of patients (29/32) in group II, and 67% of patients (4/6) in group III. Three patients (3.5%) had complications of omental mobilization. Four patients (4.7%) died after the operation as a result of failure of the omentum to manage the problem for which it was used. Conclusions: Results with omental transposition compare favorably with published series of similarly challenging cases managed with muscle transposition. Complications of omental mobilization are rare. We believe that its unique properties render the omentum an excellent choice of vascularized pedicle in the management of the most complex cardiothoracic surgical problems.J Thorac Cardiovasc Surg 2003;125:526-3

Keeping the collectivity in mind?

The key question in this three way debate is the role of the collectivity and of agency. Collins and Shrager debate whether cognitive psychology has, like the sociology of knowledge, always taken the mind to extend beyond the individual. They agree that irrespective of the history, socialization is key to understanding the mind and that this is compatible with Clark’s position; the novelty in Clark’s “extended mind” position appears to be the role of the material rather than the role of other minds. Collins and Clark debate the relationship between self, agency, and the human collectivity. Collins argues that the Clark’s extended mind fails to stress the asymmetry of the relationship between the self and its material “scaffolding.” Clark accepts that there is asymmetry but that an asymmetrical ensemble is sufficient to explain the self. Collins says that we know too little about the material world to pursue such a model to the exclusion of other approaches including that both the collectivity and language have agency. The collectivity must be kept in mind! (Though what follows is a robust exchange of views it is also a cooperative effort, authors communicating “backstage” with each other to try to make the disagreements as clear and to the point as possible.

Bioengineered constructs combined with exercise enhance stem cell-mediated treatment of volumetric muscle loss

Volumetric muscle loss (VML) is associated with loss of skeletal muscle function, and current treatments show limited efficacy. Here we show that bioconstructs suffused with genetically-labelled muscle stem cells (MuSCs) and other muscle resident cells (MRCs) are effective to treat VML injuries in mice. Imaging of bioconstructs implanted in damaged muscles indicates MuSCs survival and growth, and ex vivo analyses show force restoration of treated muscles. Histological analysis highlights myofibre formation, neovascularisation, but insufficient innervation. Both innervation and in vivo force production are enhanced when implantation of bioconstructs is followed by an exercise regimen. Significant improvements are also observed when bioconstructs are used to treat chronic VML injury models. Finally, we demonstrate that bioconstructs made with human MuSCs and MRCs can generate functional muscle tissue in our VML model. These data suggest that stem cell-based therapies aimed to engineer tissue in vivo may be effective to treat acute and chronic VML

Adding a Little Reality to Building Ontologies for Biology

BACKGROUND: Many areas of biology are open to mathematical and computational modelling. The application of discrete, logical formalisms defines the field of biomedical ontologies. Ontologies have been put to many uses in bioinformatics. The most widespread is for description of entities about which data have been collected, allowing integration and analysis across multiple resources. There are now over 60 ontologies in active use, increasingly developed as large, international collaborations. There are, however, many opinions on how ontologies should be authored; that is, what is appropriate for representation. Recently, a common opinion has been the "realist" approach that places restrictions upon the style of modelling considered to be appropriate. METHODOLOGY/PRINCIPAL FINDINGS: Here, we use a number of case studies for describing the results of biological experiments. We investigate the ways in which these could be represented using both realist and non-realist approaches; we consider the limitations and advantages of each of these models. CONCLUSIONS/SIGNIFICANCE: From our analysis, we conclude that while realist principles may enable straight-forward modelling for some topics, there are crucial aspects of science and the phenomena it studies that do not fit into this approach; realism appears to be over-simplistic which, perversely, results in overly complex ontological models. We suggest that it is impossible to avoid compromise in modelling ontology; a clearer understanding of these compromises will better enable appropriate modelling, fulfilling the many needs for discrete mathematical models within computational biology

Contested Collective Intelligence: rationale, technologies, and a human-machine annotation study

We propose the concept of Contested Collective Intelligence (CCI) as a distinctive subset of the broader Collective Intelligence design space. CCI is relevant to the many organizational contexts in which it is important to work with contested knowledge, for instance, due to different intellectual traditions, competing organizational objectives, information overload or ambiguous environmental signals. The CCI challenge is to design sociotechnical infrastructures to augment such organizational capability. Since documents are often the starting points for contested discourse, and discourse markers provide a powerful cue to the presence of claims, contrasting ideas and argumentation, discourse and rhetoric provide an annotation focus in our approach to CCI. Research in sensemaking, computer-supported discourse and rhetorical text analysis motivate a conceptual framework for the combined human and machine annotation of texts with this specific focus. This conception is explored through two tools: a social-semantic web application for human annotation and knowledge mapping (Cohere), plus the discourse analysis component in a textual analysis software tool (Xerox Incremental Parser: XIP). As a step towards an integrated platform, we report a case study in which a document corpus underwent independent human and machine analysis, providing quantitative and qualitative insight into their respective contributions. A promising finding is that significant contributions were signalled by authors via explicit rhetorical moves, which both human analysts and XIP could readily identify. Since working with contested knowledge is at the heart of CCI, the evidence that automatic detection of contrasting ideas in texts is possible through rhetorical discourse analysis is progress towards the effective use of automatic discourse analysis in the CCI framework

Impaired Representation of Geometric Relationships in Humans with Damage to the Hippocampal Formation

The pivotal role of the hippocampus for spatial memory is well-established. However, while neurophysiological and imaging studies suggest a specialization of the hippocampus for viewpoint-independent or allocentric memory, results from human lesion studies have been less conclusive. It is currently unclear whether disproportionate impairment in allocentric memory tasks reflects impairment of cognitive functions that are not sufficiently supported by regions outside the medial temporal lobe or whether the deficits observed in some studies are due to experimental factors. Here, we have investigated whether hippocampal contributions to spatial memory depend on the spatial references that are available in a certain behavioral context. Patients with medial temporal lobe lesions affecting systematically the right hippocampal formation performed a series of three oculomotor tasks that required memory of a spatial cue either in retinal coordinates or relative to a single environmental reference across a delay of 5000 ms. Stimulus displays varied the availability of spatial references and contained no complex visuo-spatial associations. Patients showed a selective impairment in a condition that critically depended on memory of the geometric relationship between spatial cue and environmental reference. We infer that regions of the medial temporal lobe, most likely the hippocampal formation, contribute to behavior in conditions that exceed the potential of viewpoint-dependent or egocentric representations. Apparently, this already applies to short-term memory of simple geometric relationships and does not necessarily depend on task difficulty or integration of landmarks into more complex representations. Deficient memory of basic geometric relationships may represent a core deficit that contributes to impaired performance in allocentric spatial memory tasks

Item-location binding in working memory: Is it hippocampus-dependent?

A general consensus is emerging that the hippocampus has an important and active role in the creation of new long-term memory representations of associations or bindings between elements. However, it is less clear whether this contribution can be extended to the creation of temporary bound representations in working memory, involving the retention of small numbers of items over short delays. We examined this by administering a series of recognition and recall tests of working memory for color-location binding and object-location binding to a patient with highly selective hippocampal damage (Jon), and groups of control participants. Jon achieved high levels of accuracy in all working memory tests of recognition and recall binding across retention intervals of up to 10 seconds. In contrast, Jon performed at chance on an unexpected delayed test of the same object-location binding information. These findings indicate a clear dissociation between working memory and long-term memory, with no evidence for a critical hippocampal contribution to item-location binding in working memory

Myosin heavy chain and physiological adaptation of the rat diaphragm in elastase-induced emphysema

BACKGROUND: Several physiological adaptations occur in the respiratory muscles in rodent models of elastase-induced emphysema. Although the contractile properties of the diaphragm are altered in a way that suggests expression of slower isoforms of myosin heavy chain (MHC), it has been difficult to demonstrate a shift in MHCs in an animal model that corresponds to the shift toward slower MHCs seen in human emphysema. METHODS: We sought to identify MHC and corresponding physiological changes in the diaphragms of rats with elastase-induced emphysema. Nine rats with emphysema and 11 control rats were studied 10 months after instillation with elastase. MHC isoform composition was determined by both reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry by using specific probes able to identify all known adult isoforms. Physiological adaptation was studied on diaphragm strips stimulated in vitro. RESULTS: In addition to confirming that emphysematous diaphragm has a decreased fatigability, we identified a significantly longer time-to-peak-tension (63.9 ± 2.7 ms versus 53.9 ± 2.4 ms). At both the RNA (RT-PCR) and protein (immunocytochemistry) levels, we found a significant decrease in the fastest, MHC isoform (IIb) in emphysema. CONCLUSION: This is the first demonstration of MHC shifts and corresponding physiological changes in the diaphragm in an animal model of emphysema. It is established that rodent emphysema, like human emphysema, does result in a physiologically significant shift toward slower diaphragmatic MHC isoforms. In the rat, this occurs at the faster end of the MHC spectrum than in humans