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\"David Lynch is best known for his work as a filmmaker, directing some of the most iconic movies in American history. His output as a visual artist is less widely known. This revelatory book brings together some of the most striking examples of Lynch's paintings, drawings, photographs, installations, film stills, and sculptures. Many of these works reveal the dark underpinnings behind Lynch's often macabre films and television series. Others explore his fascination with texture and collage. Edited by Stijn Huijts and introduced by David Lynch's biographer, Krinstine McKenna, along with insightful texts by Michael Chabon and Petra Giloy-Hirtz. This book reveals an unexplored facet of Lynch's oeuvre and affirms that he is as brilliant a visual artist as he is a filmmaker.\" --publisher's description, lower cover.

Mesenchymal stem cells (MSCs) and macrophages are fundamental components of the stem cell niche and function coordinately to regulate haematopoietic stem cell self-renewal and mobilization. Recent studies indicate that mitophagy and healthy mitochondrial function are critical to the survival of stem cells, but how these processes are regulated in MSCs is unknown. Here we show that MSCs manage intracellular oxidative stress by targeting depolarized mitochondria to the plasma membrane via arrestin domain-containing protein 1-mediated microvesicles. The vesicles are then engulfed and re-utilized via a process involving fusion by macrophages, resulting in enhanced bioenergetics. Furthermore, we show that MSCs simultaneously shed micro RNA-containing exosomes that inhibit macrophage activation by suppressing Toll-like receptor signalling, thereby de-sensitizing macrophages to the ingested mitochondria. Collectively, these studies mechanistically link mitophagy and MSC survival with macrophage function, thereby providing a physiologically relevant context for the innate immunomodulatory activity of MSCs. The physiological role of crosstalk between mesenchymal stem cells (MSC) and macrophages is unclear. Here, Phinney et al . show that MSCs transfer mitochondria to macrophages under oxidative stress, and desensitize macrophages to mitochondria by using microvesicles to repress Toll receptor signalling.

\"Here begins Arthur Curry's recollection of the epic journey that led him to become the mythical superhero we know as Aquaman. Since his dramatic debut in the 1940s, Aquaman has gone from admired hero to legendary icon. Able to breathe in both air and water, the King of the Seven Seas has fought villainy from the deepest depths of the oceans to the outer limits of the galaxy. He is unquestionably one of the greatest heroes the world has ever seen, but his rise to power was not easy.\"-- Provided by publisher.

Abstract Rationale Mesenchymal stem cells secrete paracrine factors that can regulate lung permeability and decrease inflammation, making it a potentially attractive therapy for acute lung injury. However, concerns exist whether mesenchymal stem cells’ immunomodulatory properties may have detrimental effects if targeted toward infectious causes of lung injury. Objectives Therefore, we tested the effect of mesenchymal stem cells on lung fluid balance, acute inflammation, and bacterial clearance. Methods We developed an Escherichia coli pneumonia model in our ex vivo perfused human lung to test the therapeutic effects of mesenchymal stem cells on bacterial-induced acute lung injury. Measurements and Main Results Clinical-grade human mesenchymal stem cells restored alveolar fluid clearance to a normal level, decreased inflammation, and were associated with increased bacterial killing and reduced bacteremia, in part through increased alveolar macrophage phagocytosis and secretion of antimicrobial factors. Keratinocyte growth factor, a soluble factor secreted by mesenchymal stem cells, duplicated most of the antimicrobial effects. In subsequent in vitro studies, we discovered that human monocytes expressed the keratinocyte growth factor receptor, and that keratinocyte growth factor decreased apoptosis of human monocytes through AKT phosphorylation, an effect that increased bacterial clearance. Inhibition of keratinocyte growth factor by a neutralizing antibody reduced the antimicrobial effects of mesenchymal stem cells in the ex vivo perfused human lung and monocytes grown in vitro injured with E. coli bacteria. Conclusions In E. coli–injured human lungs, mesenchymal stem cells restored alveolar fluid clearance, reduced inflammation, and exerted antimicrobial activity, in part through keratinocyte growth factor secretion.

This commentary provides a brief overview of the steps necessary for the generation of an induced pluripotent stem (iPS) cell‐derived clinical grade product. This process requires extensive, proper documentation as well as a thoughtful and systematic optimization of the manufacturing methods to ensure maintenance of the key biological features of the product, compliance with current good manufacturing practices (cGMP), and most importantly patient safety. The scale‐up and optimization also ideally include the identification of efficient and cost‐effective purification/isolation and expansion of the target cell population. Graphical Abstract This Commentary discusses the production process of an induced pluripotent stem cell‐derived clinical grade therapeutic – from bench to bedside.

The effect of systemic administration of conditioned media (CM) and extracellular vesicles (EVs) from both human and mouse bone marrow‐derived mesenchymal stromal cells (MSCs) in a murine model of severe experimental asthma was studied. Systemic administration of CM and the isolated EVs significantly ameliorated the challenge‐induced increases in airway hyperreactivity, lung inflammation, and antigen‐specific CD4 T‐cell phenotype. EVs isolated from human MSCs generally were more potent than those from mouse MSCs. An increasing number of studies demonstrate that administration of either conditioned media (CM) or extracellular vesicles (EVs) released by mesenchymal stromal cells (MSCs) derived from bone marrow and other sources are as effective as the MSCs themselves in mitigating inflammation and injury. The goal of the current study was to determine whether xenogeneic administration of CM or EVs from human bone marrow‐derived MSCs would be effective in a model of mixed Th2/Th17, neutrophilic‐mediated allergic airway inflammation, reflective of severe refractory asthma, induced by repeated mucosal exposure to Aspergillus hyphal extract (AHE) in immunocompetent C57Bl/6 mice. Systemic administration of both CM and EVs isolated from human and murine MSCs, but not human lung fibroblasts, at the onset of antigen challenge in previously sensitized mice significantly ameliorated the AHE‐provoked increases in airway hyperreactivity (AHR), lung inflammation, and the antigen‐specific CD4 T‐cell Th2 and Th17 phenotype. Notably, both CM and EVs from human MSCs (hMSCs) were generally more potent than those from mouse MSCs (mMSCs) in most of the outcome measures. The weak cross‐linking agent 1‐ethyl‐3‐[3‐dimethylaminopropyl]carbodiimide hydrochloride was found to inhibit release of both soluble mediators and EVs, fully negating effects of systemically administered hMSCs but only partly inhibited the ameliorating effects of mMSCs. These results demonstrate potent xenogeneic effects of CM and EVs from hMSCs in an immunocompetent mouse model of allergic airway inflammation and they also show differences in mechanisms of action of hMSCs versus mMSCs to mitigate AHR and lung inflammation in this model. Significance There is a growing experience demonstrating benefit of mesenchymal stromal cell (MSC)‐based cell therapies in preclinical models of asthma. In the current study, conditioned media (CM) and, in particular, the extracellular vesicle fraction obtained from the CM were as potent as the MSCs themselves in mitigating Th2/Th17‐mediated allergic airway inflammation in a mouse model of severe refractory clinical asthma. Moreover, human MSC CM and extracellular vesicles were effective in this immunocompetent mouse model. These data add to a growing scientific basis for initiating clinical trials of MSCs or extracellular vesicles derived from MSCs in severe refractory asthma and provide further insight into the mechanisms by which the MSCs may ameliorate the asthma.

Background: The optimal management of patients diagnosed in the mid-gestation with a low-lying placenta (LLP) is controversial. We sought to determine the rate of adverse pregnancy outcomes with an initial diagnosis of LLP, and whether this was dependent on a follow up sonographic diagnosis of resolution or the initial placenta-to-internal os distance (P-IOD). Methods: A retrospective cross-sectional study of singleton pregnancies with a sonographically diagnosed LLP between 18–24 weeks’ gestation (12/2010 to 7/2018) was conducted at a tertiary referral center in the U.S. Follow-up ultrasound examinations from the late second or early third trimester were reviewed. Maternal morbidity associated with blood loss, regardless of resolution of LLP was recorded and stratified by P-IOD at diagnosis. The LLP was considered resolved if the P-IOD was≥ 2.0 cm by 34 weeks’ gestation . Proportions of resolution, admissions for antepartum bleeding, preterm delivery, mode of delivery, neonatal morbidity and preterm delivery were obtained. Data was analyzed by comparing categorical variables via Chi-squared test, and continuous variables using Student t-test and analysis of variance (ANOVA). Results: Five hundred three pregnancies met inclusion criteria. All except two LLPs resolved by 34 weeks’ gestation (99.6% resolution rate). There were 40 patients who did not have a follow up ultrasound. Overall rates of hemorrhage and blood transfusion were greater than the general population. The rate of maternal hemorrhage between resolved, unresolved, unknown groups, and initial P-IOD was not significantly different. The odds of admission for antepartum bleeding were significantly greater if the P-IOD was<0.5 cm. An increase in neonatal acidosis was found in the group with initial P-IOD<0.5 cm, despite 100% resolution at time of delivery. Conclusions: The diagnosis of an LLP at 18–24 weeks’ gestation despite a high rate of resolution, is associated with an increased risk for maternal hemorrhage. LLP may be an independent risk factor for hemorrhage, regardless of the initial P-IOD or resolution. Clinicians and patients should be aware of this risk and prepared to manage adverse events.

Purpose The hypothesis was fetal sex determination by ultrasound at 11–14 weeks’ gestation has sufficient accuracy to be clinically relevant. Methods Fetal sex assessment by transabdominal ultrasound was performed in 567 fetuses at 11–14 weeks’ gestation (CRL: 45–84 mm). A mid-sagittal view of the genital region was obtained. The angle of the genital tubercle to a horizontal line through the lumbosacral skin surface was measured. The fetus was assigned male sex if the angle was > 30°, and female sex if the genital tubercle was parallel or convergent (< 10°). At an intermediate angle of 10–30°, the sex was not assigned. The results were divided into three categories based on gestational age: 11 + 2 to 12 + 1, 12 + 2 to 13 + 1, and 13 + 2 to 14 + 1 weeks’ gestation. To establish its accuracy, the first trimester fetal sex determination was compared to fetal sex determined on a mid-second trimester ultrasound. Results Sex assignment was successful in 534/683 (78%) of the cases. The overall accuracy of fetal sex assignment across all gestational ages studied was 94.4%. It was 88.3%, 94.7%, and 98.6% at 11 + 2 to 12 + 1, 12 + 2 to 13 + 1, and 13 + 2 to 14 + 1 weeks’ gestation, respectively. Conclusion Prenatal sex assignment at the time of first trimester ultrasound screening has a high accuracy rate. The accuracy improved with increasing gestational age, which suggests that if clinically important decisions, such as chorionic villus sampling, are to be made based on fetal sex, they should be delayed until the latter part of the first trimester.