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Background: The frequent occurrence of thromboembolic cerebral events continues to limit the widespread implementation of Ventricular Assist Devices (VAD) despite continued advancements in VAD design and anti-coagulation treatments. Recent studies point to the optimal positioning of the outflow graft (OG) as a potential mitigator of post implantation thromboembolism., Objective: This study aims to examine the tailoring of the OG implantation orientation with the goal of minimizing the number of thrombi reaching the cerebral vessels by means of a formal shape optimization scheme incorporated into a multi-scale hemodynamics analysis., Methods: A 3-D patient-specific computational fluid dynamics model is loosely coupled in a two-way manner to a 0-D lumped parameter model of the peripheral circulation. A Lagrangian particle-tracking scheme models and tracks thrombi as non-interacting solid spheres. The loose coupling between CFD and LPM is integrated into a geometric shape optimization scheme which aims to optimize an objective function that targets a drop in cerebral embolization, and an overall reduction in particle residence times., Results: The results elucidate the importance of OG anastomosis orientation and placement particularly in the case that studied particle release from the OG, as a fivefold decrease in cerebral embolization was observed between the optimal and non-optimal implantations. Another case considered particle release from the ventricle and aortic root walls, in which optimal implantation was achieved with a shallow insertion angle. Particle release from all three origins was investigated in the third case, demonstrating that the optimal configurations were generally characterized by VAD flow directed along the central lumen of the aortic arch. Because optimal configurations depended on the anatomic origin of the thrombus, it is important to determine, in clinical studies, the most likely sites of thrombus formation in VAD patients., Competing Interests: Declaration of Competing Interest Abubakar Dankano, Ray Prather, Blake Lozinski, Eduardo Divo: none declared. Alain Kassab has received research Grant number 18TPA34230091 from the American Heart Association as PI. William DeCampli has received research Grant number 18TPA34230091 from the American Heart Association as CoPI., (Copyright © 2024. Published by Elsevier Ltd.)

Multiple sclerosis is an inflammatory and demyelinating disease of the central nervous system. While remyelination facilitates functional recovery in animal models, it is limited in people with multiple sclerosis. Thus, multiple strategies have been put forth to promote remyelination, including exercise and medication. Exercise promotes the release of growth factors and induces protein-level changes, while remyelinating medications act through a variety of mechanisms to promote oligodendrocyte maturation within the lesion. In animal models, the combination of medication and exercise (Medication + eXercise = MedXercise) has an additive effect on remyelination and other pathological features of multiple sclerosis. In this review, we highlight the existing literature on the effects of exercise and medication on remyelination both independently and in combination., Competing Interests: Conflict of interest statement Nothing declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Maternal factors predetermine offspring development and health, including the establishment of offsprings' first microbiomes. Research in swine has shown that early microbial exposures impact microbiome colonization in piglets, but this phenomenon has never been tested in the context of delivery room disinfection. Thus, we exposed gestating sows to two delivery environments ( n  = 3/environment): stalls cleaned with a broad-spectrum disinfectant (disinfected environment [D]) or stalls cleaned only with hot-water power washing (nondisinfected environment [Nde]), 3 days prior to farrowing. Microbiomes of sows and farrowed piglets ( n  = 27/environment) were profiled at 4 different time points from birth to weaning via 16S rRNA sequencing. The results show that although vaginal, milk, skin, and gut microbiomes in mothers were minimally affected, sanitation of farrowing stalls impacted piglet microbiome colonization. These effects were mainly characterized by lower bacterial diversity in the gut and nasal cavity, specifically in D piglets at birth, and by distinct taxonomic compositions from birth to weaning depending on the farrowing environment. For instance, environmental bacteria greatly influenced microbiome colonization in Nde piglets, which also harbored significantly higher abundances of gut Lactobacillus and nasal Enhydrobacter at several time points through weaning. Different sanitation strategies at birth also resulted in distinct microbiome assembly patterns, with lower microbial exposures in D piglets being associated with limited interactions between bacterial taxa. However, increasing microbial exposures at birth through the lack of disinfection were also associated with lower piglet weight, highlighting the importance of understanding the trade-offs among optimal microbiome development, health, and growth performance in swine production systems. IMPORTANCE We show that levels of disinfection in farrowing facilities can impact early microbial exposures and colonization by pioneer microbes in piglets. Although previous research has shown a similar effect by raising pigs outdoors or by exposing them to soil, these practices are unattainable in most swine production systems in the United States due to biosecurity practices. Thus, our results underscore the importance of evaluating different disinfection practices in swine production to safely reduce pathogenic risks without limiting early microbial exposures. Allowing early exposure to both beneficial and pathogenic microbes may positively impact immune responses, reduce the stressors of weaning, and potentially reduce the need for dietary antimicrobials. However, the benefits of modified early microbial exposures need to be accomplished along with acceptable growth performance. Thus, our results also provide clues for understanding how disinfection practices in farrowing rooms may impact early microbiome development and assembly.

The article Niacin‑mediated rejuvenation of macrophage/microglia enhances remyelination of the aging central nervous system, written by Khalil S. Rawji, Adam M.H. Young, Tanay Ghosh, Nathan J. Michaels, Reza Mirzaei, Janson Kappen, Kathleen L. Kolehmainen, Nima Alaeiilkhchi, Brian Lozinski, Manoj K. Mishra, Annie Pu, Weiwen Tang, Salma Zein, Deepak K. Kaushik, Michael B. Keough, Jason R. Plemel, Fiona Calvert, Andrew J. Knights, Daniel J. Gaffney, Wolfram Tetzlaff, Robin J. M. Franklin and V. Wee Yong, was originally published electronically on the publisher's internet.

Remyelination following CNS demyelination restores rapid signal propagation and protects axons; however, its efficiency declines with increasing age. Both intrinsic changes in the oligodendrocyte progenitor cell population and extrinsic factors in the lesion microenvironment of older subjects contribute to this decline. Microglia and monocyte-derived macrophages are critical for successful remyelination, releasing growth factors and clearing inhibitory myelin debris. Several studies have implicated delayed recruitment of macrophages/microglia into lesions as a key contributor to the decline in remyelination observed in older subjects. Here we show that the decreased expression of the scavenger receptor CD36 of aging mouse microglia and human microglia in culture underlies their reduced phagocytic activity. Overexpression of CD36 in cultured microglia rescues the deficit in phagocytosis of myelin debris. By screening for clinically approved agents that stimulate macrophages/microglia, we have found that niacin (vitamin B3) upregulates CD36 expression and enhances myelin phagocytosis by microglia in culture. This increase in myelin phagocytosis is mediated through the niacin receptor (hydroxycarboxylic acid receptor 2). Genetic fate mapping and multiphoton live imaging show that systemic treatment of 9-12-month-old demyelinated mice with therapeutically relevant doses of niacin promotes myelin debris clearance in lesions by both peripherally derived macrophages and microglia. This is accompanied by enhancement of oligodendrocyte progenitor cell numbers and by improved remyelination in the treated mice. Niacin represents a safe and translationally amenable regenerative therapy for chronic demyelinating diseases such as multiple sclerosis.

Multiple sclerosis (MS) is a central nervous system (CNS) disorder characterized by inflammation, demyelination, and neurodegeneration. Emerging research suggests that exercise has therapeutic benefits for MS patients but the clinical data have focused primarily on non-CNS outcomes. In this review, we discuss evidence in preclinical MS models that exercise influences oligodendrocyte proliferation and repopulation, remyelination, neuroinflammation, neuroprotection, axonal regeneration, and astrogliosis. Evidence for the therapeutic effects of exercise in MS is further supplemented by data from other CNS diseases, including Alzheimer's disease, Parkinson's disease, and spinal cord injury. These results motivate studies into the benefits that exercise confers within the CNS in MS., (© 2019 Wiley Periodicals, Inc.)

Background: Earlier clinical reports have identified femoral anteversion as a factor associated with developmental dysplasia of the hip. This study investigates the biomechanical influence of femoral anteversion on severe dislocations and its effect on hip reduction using the Pavlik harness., Methods: A computational model of an infant lower-extremity, representing a ten-week old female was used to analyze the biomechanics of anteversion angles ranging from 30° to 70° when severe dislocation was being treated with the Pavlik harness. Specifically, the effects and relationships between muscle passive response and femoral anteversion angle were investigated over a range of hip abduction and external rotation., Findings: Results of this study suggest that increased femoral anteversion may decrease the success rate for treatment of high-grade developmental dysplasia of the hip when using the Pavlik harness. However, hip external rotation and decreased abduction in the harness may facilitate initial reduction in these cases., Interpretation: This biomechanical study may help explain why dissections of newborn specimen with developmental dysplasia of the hip have shown normal distribution of femoral anteversion in contrast to studies of patients requiring surgery where greater frequency of increased femoral anteversion has been reported. This study also suggests that adjusting the Pavlik harness to increase external hip rotation and decrease hip abduction may facilitate initial reduction for severe dislocations with increased femoral anteversion., Competing Interests: Declaration of competing interest Authors declare that they have no conflict of interest., (Copyright © 2019. Published by Elsevier Ltd.)