Virtual stenting workflow with vessel-specific initialization and adaptive expansion for neurovascular stents and flow diverters

Endovascular intervention using traditional neurovascular stents and densely braided flow diverters (FDs) have become the preferred treatment strategies for traditionally challenging intracranial aneurysms. Modeling stent and FD deployment in patient-specific aneurysms and its flow modification results prior to the actual intervention can potentially predict the patient outcome and treatment optimization. We present a clinically focused, streamlined virtual stenting workflow that efficiently simulates stent and FD treatment in patient-specific aneurysms based on expanding a simplex mesh structure. The simplex mesh is generated using an innovative vessel-specific initialization technique, which uses the patient’s parent artery diameter to identify the initial position of the simplex mesh inside the artery. A novel adaptive expansion algorithm enables the acceleration of deployment process by adjusting the expansion forces based on the distance of the simplex mesh from the parent vessel. The virtual stenting workflow was tested by modeling the treatment of two patient-specific aneurysms using the Enterprise stent and the Pipeline Embolization Device (commercial FD). Both devices were deployed in the aneurysm models in a few seconds. Computational fluid dynamics analyses of pre- and post-treatment aneurysmal hemodynamics show flow reduction in the aneurysmal sac in treated aneurysms, with the FD diverting more flow than the Enterprise stent. The test results show that this workflow can rapidly simulate clinical deployment of stents and FDs, hence paving the way for its future clinical implementation.     

Takeoff temperatures in Melitaea cinxia butterflies from latitudinal and elevational range limits: a potential adaptation to solar irradiance

1. This study provides evidence that a heliophilic butterfly, the Glanville fritillary (Melitaea cinxia) has adapted differently to environmental variation across latitudes and elevations. 2. In cool air, basking M. cinxia orient themselves perpendicular to the sun's rays to gain heat and take off. During flight, solar heating is reduced because orientation perpendicular to the sun is no longer possible and convective cooling occurs. Consequently, M. cinxia have been shown to suffer net heat loss in flight, even in full sunshine. When flight duration is restricted in this way, the takeoff temperature becomes an important thermal adaptation. 3. Using a thermal imaging camera, takeoff temperatures were measured in experimental butterflies. Butterflies from the northern range limit in Finland took flight at slightly hotter temperatures than butterflies from the southern limit in Spain, and much hotter than butterflies from the elevational limit (1900–2300 m) in the French Alps. Butterflies from low‐elevation populations in southern France also took off much hotter than did the nearby Alpine population. 4. These results suggest that the influence of elevation is different from that of latitude in more respects than ambient temperature. Values of solar irradiance in the butterflies' flight season in each region show that insects from the coolest habitats, Finland and the Alps, experienced similar solar irradiance during basking, but that Finns experienced much lower irradiance in flight. This difference may have favored Finnish butterflies evolving higher takeoff temperatures than Alpine butterflies that also flew in cool air but benefited from more intense radiant energy after takeoff.     

Biopsychosocial Factors and Cognitive Function in Cat Ownership and Attachment in Community-dwelling Older Adults

ABSTRACT

Few studies consider the health benefits of pet ownership from a biopsychosocial perspective, and a paucity of studies investigate cat ownership. The current study was designed to determine if psychosocial factors (stress, loneliness, and depression), biological levels of stress and inflammation (salivary cortisol, interleukin-1β, and C-reactive protein [CRP]), and cognitive function were associated with companion cat ownership/attachment in community-dwelling older adults. Community-dwelling older adults (n = 96, mean age = 76.6 years) who either owned a cat and no dog (n = 41) or owned neither a cat nor a dog (n = 55) completed questionnaires (Perceived Stress Scale, Revised–UCLA Loneliness Scale, Geriatric Depression Scale-Short Form, Montreal Cognitive Assessment, and Lexington Attachment to Pets Scale) and provided saliva specimens which were assayed for stress and inflammatory biomarkers. The majority of participants screened positive for mild cognitive impairment, reported low levels of stress, loneliness, and depression, and the biomarkers reflected fairly low levels of stress and inflammation. Binary logistic regression analysis revealed that psychosocial factors, salivary biomarkers, and cognitive function were not significantly associated with cat ownership. Age was the only significant predictor of cat ownership (OR = 0.92, p < 0.01) with the odds of cat ownership decreasing by 8.3% per year of advancing age. On average, cat owners were “somewhat attached” to their cats; however, 26% were “strongly attached” to their cats. Correlation analyses revealed the level of attachment to cats was not associated with study outcomes. These results show that cat ownership declined with each advancing year, which lessens the opportunity for older adults to form attachment bonds. The level of pet attachment supports the consideration of cats as a source of an attachment relationship for older adults, including those with cognitive impairment.     

Tapping the therapeutic potential of protein tyrosine phosphatase 4A with small molecule inhibitors

Protein tyrosine phosphatases (PTPs) are emerging new targets for drug discovery. PTPs and protein tyrosine kinases (PTKs) maintain cellular homeostasis through opposing roles: tyrosine O-dephosphorylation and -phosphorylation, respectively. An imbalance in the phosphorylation equilibrium results in aberrant protein signaling and pathophysiological conditions. PTPs have historically been considered ‘undruggable’, in part due to a lack of evidence defining their relationship to disease causality and a focus on purely competitive inhibitors. However, a better understanding of protein–protein interfaces and shallow active sites has recently renewed interest in the pursuit of allosteric and orthosteric modulators of targets outside the major druggable protein families. While their biological mechanism of action still remains to be clarified, PTP4A1–3 (also referred to as PRL1-3) are validated oncology targets and play an important role in cell proliferation, metastasis, and tumor angiogenesis. In this Digest, recent syntheses and structure-activity relationships (SAR) of small molecule inhibitors (SMIs) of PTP4A1–3 are summarized, and enzyme docking studies of the most potent chemotype are highlighted. In particular, the thienopyridone scaffold has emerged as a potent lead structure to interrogate the function and druggability of this dual-specificity PTP.     

The bacterial virulence factor NleA inhibits cellular protein secretion by disrupting mammalian COPII function

Enterohemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) maintain an extracellular lifestyle and use a type III secretion system to translocate effector proteins into the host cytosol. These effectors manipulate host pathways to favor bacterial replication and survival. NleA is an EHEC/EPEC- and related species-specific translocated effector protein that is essential for bacterial virulence. However, the mechanism by which NleA impacts virulence remains undetermined. Here we demonstrate that NleA compromises the Sec23/24 complex, a component of the mammalian COPII protein coat that shapes intracellular protein transport vesicles, by directly binding Sec24. Expression of an NleA-GFP fusion protein reduces the efficiency of cellular secretion by 50%, and secretion is inhibited in EPEC-infected cells. Direct biochemical experiments show that NleA inhibits COPII-dependent protein export from the endoplasmic reticulum. Collectively, these findings indicate that disruption of COPII function in host cells contributes to the virulence of EPEC and EHEC.     

Electrical conductivity in a mixed-species biofilm

Geobacter sulfurreducens can form electrically conductive biofilms, but the potential for conductivity through mixed-species biofilms has not been examined. A current-producing biofilm grown from a wastewater sludge inoculum was highly conductive with low charge transfer resistance even though microorganisms other than Geobacteraceae accounted for nearly half the microbial community.