Effect of Laparoscopic-assisted Gastropexy on Gastrointestinal Transit Time in Dogs.

BackgroundProphylactic gastropexy has been promoted as a means of preventing gastric volvulus during gastric dilatation and volvulus (GDV) syndrome. Little is known about the impact of gastropexy on gastrointestinal transit time.HypothesisLaparoscopic-assisted gastropexy (LAG) will not alter gastrointestinal transit times when comparing gastric (GET), small and large bowel (SLBTT), and whole gut transit times (TTT) before and after surgery.Animals10 healthy client-owned large-breed dogs.MethodsProspective clinical trial. Before surgery, all dogs underwent physical examination and diagnostic evaluation to ensure normal health status. Dogs were fed a prescription diet for 6 weeks before determination of gastrointestinal transit with a wireless motility capsule. LAG was then performed, and dogs were fed the diet for 6 additional weeks. Measurement of transit times was repeated 6 weeks after surgery.ResultsTen dogs of various breeds at-risk for GDV were enrolled. No complications were encountered associated with surgery or capsule administration. There were no significant differences in GET 429 [306-1,370] versus 541 [326-1,298] (P = 0.80), SLBTT 1,243 [841-3,070] versus 1,540 [756-2,623] (P = 0.72), or TTT 1,971 [1,205-3,469] versus 1,792 [1,234-3,343] minutes (median, range) (P = 0.65) before and after LAG.Conclusions and clinical importanceAn effect of LAG on gastrointestinal transit time was not identified, and wireless motility capsule can be safely administered in dogs after LAG

Mixing and internal dynamics of droplets impacting and coalescing on a solid surface.

The coalescence and mixing of a sessile and an impacting liquid droplet on a solid surface are studied experimentally and numerically in terms of lateral separation and droplet speed. Two droplet generators are used to produce differently colored droplets. Two high-speed imaging systems are used to investigate the impact and coalescence of the droplets in color from a side view with a simultaneous gray-scale view from below. Millimeter-sized droplets were used with dynamical conditions, based on the Reynolds and Weber numbers, relevant to microfluidics and commercial inkjet printing. Experimental measurements of advancing and receding static contact angles are used to calibrate a contact angle hysteresis model within a lattice Boltzmann framework, which is shown to capture the observed dynamics qualitatively and the final droplet configuration quantitatively. Our results show that no detectable mixing occurs during impact and coalescence of similar-sized droplets, but when the sessile droplet is sufficiently larger than the impacting droplet vortex ring generation can be observed. Finally we show how a gradient of wettability on the substrate can potentially enhance mixing.This work was supported by the Engineering and Physical Sciences Research Council (Grant No. EP/H018913/, Innovation in industrial inkjet technology) and the KACST-Cambridge Research Centre.This is the accepted version of the original article published in Physical Review E and available online here: http://link.aps.org/doi/10.1103/PhysRevE.88.023023

Geometric control of myogenic cell fate.

This work combines expertise in stem cell biology and bioengineering to define the system for geometric control of proliferation and differentiation of myogenic progenitor cells. We have created an artificial niche of myogenic progenitor cells, namely, modified extracellular matrix (ECM) substrates with spatially embedded growth or differentiation factors (GF, DF) that predictably direct muscle cell fate in a geometric pattern. Embedded GF and DF signal progenitor cells from specifically defined areas on the ECM successfully competed against culture media for myogenic cell fate determination at a clearly defined boundary. Differentiation of myoblasts into myotubes is induced in growth-promoting medium, myotube formation is delayed in differentiation-promoting medium, and myogenic cells, at different stages of proliferation and differentiation, can be induced to coexist adjacently in identical culture media. This method can be used to identify molecular interactions between cells in different stages of myogenic differentiation, which are likely to be important determinants of tissue repair. The designed ECM niches can be further developed into a vehicle for transplantation of myogenic progenitor cells maintaining their regenerative potential. Additionally, this work may also serve as a general model to engineer synthetic cellular niches to harness the regenerative potential of organ stem cells

Multiple markers of cortical morphology reveal evidence of supragranular thinning in schizophrenia.

In vivo structural neuroimaging can reliably identify changes to cortical morphology and its regional variation but cannot yet relate these changes to specific cortical layers. We propose, however, that by synthesizing principles of cortical organization, including relative contributions of different layers to sulcal and gyral thickness, regional patterns of variation in thickness of different layers across the cortical sheet and profiles of layer variation across functional hierarchies, it is possible to develop indirect morphological measures as markers of more specific cytoarchitectural changes. We developed four indirect measures sensitive to changes specifically occurring in supragranular cortical layers, and applied these to test the hypothesis that supragranular layers are disproportionately affected in schizophrenia. Our findings from the four different measures converge to indicate a predominance of supragranular thinning in schizophrenia, independent of medication and illness duration. We propose that these indirect measures offer novel ways of identifying layer-specific cortical changes, offering complementary in vivo observations to existing post-mortem studies.KW is supported by the University of Cambridge MB/PhD Programme and, together with KJW, by the Wellcome Trust. IMG by a Wellcome Trust Strategic Award (RNAG/260), and LR and PCF by the Bernard Wolfe Health Neuroscience Fund and Wellcome Trust

Conservative and disruptive modes of adolescent change in human brain functional connectivity

Adolescent changes in human brain function are not entirely understood. Here, we used multiecho functional MRI (fMRI) to measure developmental change in functional connectivity (FC) of resting-state oscillations between pairs of 330 cortical regions and 16 subcortical regions in 298 healthy adolescents scanned 520 times. Participants were aged 14 to 26 y and were scanned on 1 to 3 occasions at least 6 mo apart. We found 2 distinct modes of age-related change in FC: “conservative” and “disruptive.” Conservative development was characteristic of primary cortex, which was strongly connected at 14 y and became even more connected in the period from 14 to 26 y. Disruptive development was characteristic of association cortex and subcortical regions, where connectivity was remodeled: connections that were weak at 14 y became stronger during adolescence, and connections that were strong at 14 y became weaker. These modes of development were quantified using the maturational index (MI), estimated as Spearman’s correlation between edgewise baseline FC (at 14 y, FC14) and adolescent change in FC (ΔFC14−26), at each region. Disruptive systems (with negative MI) were activated by social cognition and autobiographical memory tasks in prior fMRI data and significantly colocated with prior maps of aerobic glycolysis (AG), AG-related gene expression, postnatal cortical surface expansion, and adolescent shrinkage of cortical thickness. The presence of these 2 modes of development was robust to numerous sensitivity analyses. We conclude that human brain organization is disrupted during adolescence by remodeling of FC between association cortical and subcortical areas

Adsorption behavior of Eu(III) on partially Fe(III)- or Ti(IV)-coated silica

The adsorption behavior of Eu(III) onto silica surface, which was partially coated with Fe(III) or Ti(IV), was investigated to determine Fe(III) or Ti(IV) effects on the surface reaction of lanthanides on mineral surfaces in groundwater. Compared with a parallel uncoated silica, the Fe(III)-coated silica did not enhance the adsorption of Eu(III). However, enhanced adsorption of Eu(III) on the Ti(IV)-coated silica was observed by increasing the amount of Ti(IV) on the silica surface

AN OBLIGATORY ROLE OF MIND BOMB-1 IN NOTCH SIGNALING OF MAMMALIAN DEVELOPMENT

Background. The Notch signaling pathway is an evolutionarily conserved intercellular signaling module essential for cell fate specification that requires endocytosis of Notch ligands. Structurally distinct E3 ubiquitin ligases, Neuralized (Neur) and Mind bomb (Mib), cooperatively regulate the endocytosis of Notch ligands in Drosophila. However, the respective roles of the mammalian E3 ubiquitin ligases, Neur1, Neur2, Mib1, and Mib2, in mammalian development are poorly understood. Methodology/Principal Findings. Through extensive use of mammalian genetics, here we show that Neur1 and Neur2 double mutants and Mib2 2/2 mice were viable and grossly normal. In contrast, conditional inactivation of Mib1 in various tissues revealed the representative Notch phenotypes: defects of arterial specification as deltalike4 mutants, abnormal cerebellum and skin development as jagged1 conditional mutants, and syndactylism as jagged2 mutants. Conclusions/Significance. Our data provide the first evidence that Mib1 is essential for Jagged as well as Deltalike ligand-mediated Notch signaling in mammalian development, while Neur1, Neur2, and Mib2 are dispensable.open117978Nsciescopu

Codelivery of a cytotoxin and photosensitiser via a liposomal nanocarrier: a novel strategy for light-triggered cytosolic release

Endosomal entrapment is a key issue for the intracellular delivery of many nano-sized biotherapeutics to their cytosolic or nuclear targets. Photochemical internalisation (PCI) is a novel light-based solution that can be used to trigger the endosomal escape of a range of bioactive agents into the cytosol leading to improved efficacy in pre-clinical and clinical studies. PCI typically depends upon the endolysosomal colocalisation of the bioactive agent with a suitable photosensitiser that is administered separately. In this study we demonstrate that both these components may be combined for codelivery via a novel multifunctional liposomal nanocarrier, with a corresponding increase in the biological efficacy of the encapsulated agent. As proof of concept, we show here that the cytotoxicity of the 30 kDa protein toxin, saporin, in MC28 fibrosarcoma cells is significantly enhanced when delivered via a cell penetrating peptide (CPP)-modified liposome, with the CPP additionally functionalised with a photosensitiser that is targeted to endolysosomal membranes. This innovation opens the way for the efficient delivery of a range of biotherapeutics by the PCI approach, incorporating a clinically proven liposome delivery platform and using bioorthogonal ligation chemistries to append photosensitisers and peptides of choice

Structural mapping in statistical word problems: A relational reasoning approach to Bayesian inference

Presenting natural frequencies facilitates Bayesian inferences relative to using percentages. Nevertheless, many people, including highly educated and skilled reasoners, still fail to provide Bayesian responses to these computationally simple problems. We show that the complexity of relational reasoning (e.g., the structural mapping between the presented and requested relations) can help explain the remaining difficulties. With a non-Bayesian inference that required identical arithmetic but afforded a more direct structural mapping, performance was universally high. Furthermore, reducing the relational demands of the task through questions that directed reasoners to use the presented statistics, as compared with questions that prompted the representation of a second, similar sample, also significantly improved reasoning. Distinct error patterns were also observed between these presented- and similar-sample scenarios, which suggested differences in relational-reasoning strategies. On the other hand, while higher numeracy was associated with better Bayesian reasoning, higher-numerate reasoners were not immune to the relational complexity of the task. Together, these findings validate the relational-reasoning view of Bayesian problem solving and highlight the importance of considering not only the presented task structure, but also the complexity of the structural alignment between the presented and requested relations