Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia.

Venous bypass grafts often fail following arterial implantation due to excessive smooth muscle cells (VSMC) proliferation and consequent intimal hyperplasia (IH). Intercellular communication mediated by Connexins (Cx) regulates differentiation, growth and proliferation in various cell types. Microarray analysis of vein grafts in a model of bilateral rabbit jugular vein graft revealed Cx43 as an early upregulated gene. Additional experiments conducted using an ex-vivo human saphenous veins perfusion system (EVPS) confirmed that Cx43 was rapidly increased in human veins subjected ex-vivo to arterial hemodynamics. Cx43 knock-down by RNA interference, or adenoviral-mediated overexpression, respectively inhibited or stimulated the proliferation of primary human VSMC in vitro. Furthermore, Cx blockade with carbenoxolone or the specific Cx43 inhibitory peptide 43gap26 prevented the burst in myointimal proliferation and IH formation in human saphenous veins. Our data demonstrated that Cx43 controls proliferation and the formation of IH after arterial engraftment

Complex patterns of spontaneous initiations and terminations of reentrant circulation in a loop of cardiac tissue

A two-component model is developed that consists of a discrete loop of cardiac cells that circulates action potentials together with a cardiac pacing mechanism. Physiological properties of cells such as restitutions of refractoriness and of conduction velocity are given via experimentally measured functions. The dynamics of circulating pulses and their interactions with the pacer are regulated by two threshold relations. Patterns of spontaneous initiations and terminations of reentry (SITR) generated by this system are studied through numerical simulations and analytical observations. These patterns can be regular or irregular; causes of irregularities are identified as the threshold bistability of reentrant circulation (T-bistability) and in some cases, also phase-resetting interactions with the pacer.Comment: 27 pages, 10 figures, 61 references; A version of this paper (same results) is to appear in the Journal of Theoretical Biology; arXiv V2 adds helpful commments to facilitate reading and corrects minor errors in presentatio

Immune-Instructive Polymers Control Macrophage Phenotype and Modulate the Foreign Body Response In Vivo

© 2020 The Author(s) Implantation of medical devices can result in inflammation. A large library of polymers is screened, and a selection found to promote macrophage differentiation towards pro- or anti-inflammatory phenotypes. The bioinstructive properties of these materials are validated within a rodent model. By identifying novel materials with immune-instructive properties, the relationship between material-immune cell interactions could be investigated, and this offers exciting possibilities to design novel bioinstructive materials that can be used for numerous clinical applications including medical implants

Short-term pre-operative protein caloric restriction in elective vascular surgery patients: a randomized clinical trial

(1) Background: Vascular surgery operations are hampered by high failure rates and frequent occurrence of peri-operative cardiovascular complications. In pre-clinical studies, pre-operative restriction of proteins and/or calories (PCR) has been shown to limit ischemia-reperfusion damage, slow intimal hyperplasia, and improve metabolic fitness. However, whether these dietary regimens are feasible and safe in the vascular surgery patient population remains unknown. (2) Methods: We performed a randomized controlled trial in patients scheduled for any elective open vascular procedure. Participants were randomized in a 3:2 ratio to either four days of outpatient pre-operative PCR (30% calorie, 70% protein restriction) or their regular ad-libitum diet. Blood was drawn at baseline, pre-operative, and post-operative day 1 timepoints. A leukocyte subset flow cytometry panel was performed at these timepoints. Subcutaneous/perivascular adipose tissue was sampled and analyzed. Follow-up was one year post-op. (3) Results: 19 patients were enrolled, of whom 11 completed the study. No diet-related reasons for non-completion were reported, and there was no intervention group crossover. The PCR diet induced weight loss and BMI decrease without malnutrition. Insulin sensitivity was improved after four days of PCR (p = 0.05). Between diet groups, there were similar rates of re-intervention, wound infection, and cardiovascular complications. Leukocyte populations were maintained after four days of PCR. (4) Conclusions: Pre-operative PCR is safe and feasible in elective vascular surgery patients.Vascular Surger

Migration of chemotactic bacteria in soft agar: role of gel concentration

We study the migration of chemotactic wild-type Escherichia coli populations in semisolid (soft) agar in the concentration range C = 0.15-0.5% (w/v). For C < 0.35%, expanding bacterial colonies display characteristic chemotactic rings. At C = 0.35%, however, bacteria migrate as broad circular bands rather than sharp rings. These are growth/diffusion waves arising because of suppression of chemotaxis by the agar and have not been previously reported experimentally to our knowledge. For C = 0.4-0.5%, expanding colonies do not span the depth of the agar and develop pronounced front instabilities. The migration front speed is weakly dependent on agar concentration at C < 0.25%, but decreases sharply above this value. We discuss these observations in terms of an extended Keller-Segel model for which we derived novel transport parameter expressions accounting for perturbations of the chemotactic response by collisions with the agar. The model makes it possible to fit the observed front speed decay in the range C = 0.15-0.35%, and its solutions qualitatively reproduce the observed transition from chemotactic to growth/diffusion bands. We discuss the implications of our results for the study of bacteria in porous media and for the design of improved bacteriological chemotaxis assays.Comment: 28 pages, 5 figures. Published online at http://www.sciencedirect.com/science/article/pii/S000634951100721

Strawberry fruit resistance to simulated handling

Harvest operations are currently the main source of mechanical injury of strawberry (Fragaria x ananassa Duch.). Experiments were designed to simulate conditions encountered during commercial handling. Individual fruits were subjected to impact or compression forces with similar energy to determine the sensitivity to mechanical injury. Bruise volume was used as the measurement of injury. Bruise severity increased as a function of impact energy for both impact types. However, dropped fruits had larger bruise volume than fruits submitted to pendulum impactor at the same energy level. Doubling the impact energy (0.040 to 0.083 J) increased bruise volume by 7 times (13 to 91 mm³). Fruits dropped from 380 mm (0.075 J) showed 71% greater bruise volume than those dropped from either 130 mm (0.025 J) or 200 mm (0.040 J). Compressed fruits showed higher bruise volume than other tests. Some cultivars are more susceptible to compression forces than others. 'Sweet Charlie' berries showed bruise volume 40% higher than the others cultivars when subjected to compression. Fruits subjected to impact showed bruise volume lower than the compressed fruits, indicating the possibility to be handled and graded in a packing line.A etapa de colheita é a principal fonte de danos físicos ao morango (Fragaria x ananassa Duch.). Experimentos foram realizados para simular condições encontradas durante manuseio. Frutos foram submetidos individualmente às forças de impacto e compressão em energias similares para determinar sensibilidade dos frutos a danos físicos. Volume da injúria física foi utilizado para mensurar a incidência do dano físico ocorrido. Severidade da lesão aumenta, com incremento da energia, tanto para força de impacto como para compressão. Todavia, frutos submetidos à queda livre demonstraram maiores volumes de danos físicos do que frutos submetidos a danos ocasionados por pendulo no mesmo nível de energia. Dobrando a energia de impacto (0,040 para 0,083 J) ocorreu aumento no volume da injúria em sete vezes (13 para 91 mm³). Frutos submetidos à queda de 380 mm (0,075 J) demonstraram volumes de danos físicos 71% superiores do que aqueles ocasionados em queda de 130 mm (0,025 J) ou 200 mm (0,040 J). Frutos em teste de compressão mostraram maiores volumes de injúrias físicas do que outros testes. Alguns cultivares são mais sensíveis à força de compressão do que outros. Frutos cultivar 'Sweet Charlie' apresentaram volume de injúria 40% superiores do que outros quando submetidos à força de compressão. Morangos submetidos à força de impacto demonstraram volume de injúria inferior do que aqueles comprimidos, indicando a possibilidade dos morangos serem classificados e manuseados em uma linha de beneficiamento

Arteriopathy diagnosis in childhood arterial ischemic stroke: results of the vascular effects of infection in pediatric stroke study.

Background and purposeAlthough arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke.MethodsVascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step.ResultsCases were aged median 7.6 years (interquartile range, 2.8-14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (κ=0.77, 0.81, and 0.78).ConclusionsClinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke